Lysosome and Autophagy

This topic page reorganises the 5 source notes filed under lysosome-autophagy into reading-order axes. It does not replace the by-photo Markdown; every claim links back to a source note or the canonical transcription. Where a source carries Uncertain Spans, that uncertainty is preserved here rather than smoothed out.

Overview

The corpus’s lysosome / autophagy chapter is a small but dense late-document cluster that the rest of the JS PD pipeline cites for lysosomal-membrane biology, autophagy-pathway vocabulary, and LSD exemplars. Five overlapping axes organise the 5 sources. (1) Lysosomal enzymes, transporters, and lysosomal changes in PD — the ⊞PhReT ion-transporter / TRPM1 (MCOLN1) / TMEM175 / ATP13A2 wide matrix, a target-disease relationship bullet block, a BMs proteolytic-marker note, the RD-DDU NPC / Evox correspondence with a tier-1 / tier-2 LSD priority list, the Lysosomal changes in PD source / sample / findings table (Chu 2009, Carling 2020 fibroblast, Youn 2018), and the Cathepsin B / Cathepsin D Lysosomal Enzymes enzyme table with the cerezyme & ambroxol → cathepsin D correction note (20240722_183416). (2) Assessment of lysosome — Proteolysis / pH / Hydrolytic activity assays — the upstream Cathepsin C / Alpha-galactosidase / neuraminidase table tail, the Plasma vs Blood analyte / sample-source matrix (GBA activity / BMP / GlcSph / Cathepsin D activity / LIMP2), and the Mizushima 2020-anchored Assessment of lysosome mega-table covering short-lived / long-lived protein assays (Mazzulli 2011, Henry 2015, Jennings 2022 DNL201 AHA, Logan 2020 Denali PTV:PGRN), DQ-Red BSA, LysoTracker / LysoSensor / HCy-BIZ-BF2 NIR pH probes, magic-red Cathepsin B, p62 / SQSTM1, and AuNC nanoparticle reporters (20240722_183419). (3) Macroautophagy / Microautophagy / CMA / BMP — the LC3A / LC3B / LC3C canonical autophagy-marker block, microautophagy and CMA HSC70 / KFERQ / LAMP2A pentapeptide-recognition narrative (with the disease-associated A30P / A53T aSyn cloggs note), the HSP70 / HSC70 cf table, and the BMP (Bis(monoacylglycero)phosphate) chapter — BMP change in diseases GBA-PD / LSDs / GD / GRN-FTD / In-vivo-brain rows (Alcalay 2020, Akgoc 2015, Hein 2013, Denali PGRN_KSQ_Apr2020Update, R&D-Day LRRK2 inhibitor note), the ETV:IDS (DNL310) brain-BMP-rescue Takeda slide pair preserved as evidence, and the BMP Correction sub-block for healthy people / animal models (20240722_183423). (4) Niemann-Pick disease — NPC1 / NPC2 typing, pipeline, biomarkers — the wide Type A / Type B / Type C comparison table (Cause / MIM / Inheritance / Onset / Life expectancy / Cause of death / Systemic Sx / Neurologic Sx / prevalence / Imaging / MOA / correction / PATHOLOGY / Dx / Tx / Pipeline / outcome measure / animal model / biomarker- established / biomarker-new), the NP-C symptoms-vs-age timeline schematic and the 2013 MolGenMetabo cerebellar-volume bar chart kept as evidence, the nested NIH-Vorinostat / Orphazyme-Arimoclomol / Vtesse- VTS-270 (HP-β-CD) Phase 1/2–2/3 pipeline sub-table, the NPC-SS / 5- domain NPCCSS outcome measure, the BALB/cNctr-Npc1m1N/-J KO mouse, and the filipin / oxysterol / cholestane-3β,5α,6β-triol / 24(S)-HC / calbindin biomarker rows (20240722_184247). (5) TRPML1 — Activators, Tottori GD collaboration, Pipeline — the ML-IV / MCOLN1 LOF-mutation continuation, the Correction bullets (MK6-83 / ML-SA1 in PARK9 iPSC and L-BMAA ALS models), the Libra TFEB-translocation pipeline note, the Calporta / Merck / Haoxing Xu acquisition partial-text block, the Tottori-univ-GD CSF / serum baseline-vs-post-Ambroxol matrix (lipid: GlcCer / GalSph / BMP / GlcSph; aSyn MSD; Olink proteomics: progranulin, cathepsin S / L1 / D / B / Z / F / O / L2 / Procathepsin H, LAMP2 / LIMP2 / Beclin / P62 / LC3 / Hsp90 / Hspb1 / Hsc70 / HSPB1 / HSPB6; cytokines IL6 / IL8 / IFN-γ / CCL19 / CCL3) and the CSF-GD-vs-Ctrl Olink p-value / Log2-FC table, and the Catecholamine pathway → levodopa-pharmacology nav-vs-body drift at the bottom edge that continues onto the next photo (20240722_184542).

This topic narrates lysosome / autophagy biology and assays. Disease- side application to GBA-PD biology, GCase / substrate-pathway correction, mitophagy, parkin / pS65-Ub, microglia / inflammation, MAM / mitochondrial coupling, LRRK2 disease-side coverage, AAV / capsid / GT- safety, biomarker validation, Carling-2020 lysosomal-DEG genetics-side calls, MSA-side aSyn coverage, and α-synuclein KFERQ / Lamp2a / fibril biology lives on the relevant disease-side topic pages and is only linked here; this page does not re-narrate them.

Source Boundary / Delegation

This topic is bounded inside sections/lysosome-autophagy and does not include sources from sibling sections. Adjacent material that overlaps in content but is owned elsewhere:

boundary	adjacent material	owned by
GBA / GCase / GlcCer / GlcSph biology and the GBA-PD BMs / Cathepsin-D / cerezyme + ambroxol correction context behind the _183416 Cathepsin B / Cathepsin D table and the _183423 BMP-GBA-PD row	foundational GBA / GD / GBA-PD biochemistry (BGL activity, GBA mutation in PD, MOA hypotheses)	gba-pd-biology
GBA Activator / GBA GT / Substrate-pathway-correction modalities; PR001 / venglustat / eliglustat / ambroxol program-side application of the cathepsin-D / GlcCer / GlcSph / BMP biomarker vocabulary; the Tottori-univ-GD CSF / serum baseline-vs-post-Ambroxol matrix on _184542	GBA / GCase therapeutic modalities	gba-gcase-modalities · ambroxol · eliglustat · venglustat · pr001
α-synuclein KFERQ / LAMP2A / HSC70 CMA biology, A30P / A53T cloggs mechanism, CTSB / CTSD aSyn-fibril degradation, aSyn levels in PARK9 iPSC TRPML1-activator rescue (_183423 CMA Substrates; _183416 Cathepsin D arguments; _184542 Correction bullet)	α-synuclein synthesis (Tier 1)	alpha-synuclein
Mitophagy / PINK1 / pS65-Ub / Parkin-mediated autophagosome wrapping that the macroautophagy LC3 vocabulary on _183423 underwrites	Parkin biology / mitophagy	parkin / parkn-gt
MAM / mitochondrial coupling; MC1 / Complex I / structure / mitophagy disease-side application of the lysosomal-autophagy vocabulary	mitochondria / mitophagy / 31P MRS	mitochondria
Microglia / TNFα / CRM inflammation context; PGRN-FTD CSF BMP rows (Denali PGRN_KSQ_Apr2020Update on _183423); LRRK2 inhibitor → BMP correction (R&D-Day note on _183423); NLRP3 / pyroptosis crosstalk with autophagy	inflammation / NLRP3 / Complement / microglia	inflammation / nlrp3-inhibitor
LRRK2 disease-side coverage proper (DNL151 / DNL201 program); the Jennings 2022 #2283 DNL201 AHA labeling long-lived-protein assay on _183419 is methodology-side referenced from the program	LRRK2 pipeline	lrrk2
ETV:IDS (DNL310) brain-BMP-rescue Takeda slide pair on _183423 (TfRmu/hu / IDS KO multi-dose); AAV / capsid / promoter / route-of-administration / FDA-CTGT-2021 GT-safety vocabulary that the Niemann-Pick / TRPML1 pipeline rows imply	PK / PD / GT / pharmacology and GT Safety Appendix	pk-gt-pharmacology · molecular-biology § GT Safety Appendix (_184756)
Carling 2020 lysosomal-dysfunctional DEG VarElect / KEGG calls (CTSD, SMPD1, NPC1, …) and the variant-pathogenicity / ACMG-AMP framework; HGVS / Genotyping methodology that GBA1 / NPC1 / NPC2 calls would consume	genetics / GWAS / PRS / Pathway / variant-pathogenicity methodology	genetics-pathway · molecular-biology
[BIOMARKER] validation / qualification framework, plasma-vs-blood / serum / CSF analyte selection criteria, NfL / synaptic-change biology that the Cathepsin / BMP / LIMP2 / GlcSph biomarker rows on _183419 and _184542 would feed	biomarker validation and outcome measures	biomarkers-outcomes
MSA-side aSyn / autophagy / lysosomal coverage that mirrors the macroautophagy / CMA vocabulary	MSA pipeline	msa / msa
Catecholamine pathway → levodopa / Carbidopa / Sinemet / Madopar / COMT inhibitor / Stalevo / Wearing-off pharmacology at the bottom edge of _184542	clinical-PD pharmacology	clinical-pd
Vorinostat / Arimoclomol / 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) / Miglustat / Cyclodextrin / TRPML1-activator (MK6-83, ML-SA1) NPC1 / TRPML1 program-side coverage on _184247 and _184542	program-routing map; NPC1 / TRPML1 / Calporta-Merck rows are not promoted to entity pages in v1	therapeutic-programs § Entity Backlog Candidates
RD-DDU NPC / Evox exosome correspondence with Y.H. Park’s tier-1 / tier-2 LSD priority list (Fabry / Gaucher / Pompe / MPSII / MPSIIIA / MLD / MPSI / MPSVI / NPC) and DDU resourcing strategy on _183416	operations / DDU strategy / RD-program governance	operations

The topic also does not include the Pipeline of GD & GBA-PD lysosome cartoons / Allosteric-vs-Catalytic-site diagrams referenced in gba-gcase-modalities, the BioOrchestra biomarker chain that re-uses cathepsin / BMP analyte vocabulary (bioorchestra-biomarker-catalog), or any source filed under sibling sections — even though those pages re-use the same lysosome / autophagy / cathepsin vocabulary.

Source Coverage

5 source notes are assigned to the lysosome-autophagy section. They sit across 5 first-level nav_path clusters; the topic axes below collapse those clusters as follows:

nav root (first nav_path entry)	sources	covered axis
Lysosomal Enzymes	1	Lysosomal enzymes / transporters (⊞PhReT / TRPM1 / TMEM175 / ATP13A2), Lysosomal changes in PD evidence table, Cathepsin B / D Lysosomal Enzymes table, RD-DDU NPC correspondence
RD-DDU	1	Cathepsin C / Alpha-galactosidase / neuraminidase table tail, Plasma vs Blood analyte matrix, Mizushima-2020-anchored Assessment of lysosome mega-table
Macroautophagy	1	Macroautophagy LC3 markers · Microautophagy · CMA (HSC70 / KFERQ / LAMP2A) · BMP (Bis(monoacylglycero)phosphate) — BMP change in diseases, ETV:IDS (DNL310) slide pair as evidence, BMP Correction sub-block
Niemann-Pick disease	1	Type A / B / C wide comparison table; NPC1 / NPC2 MOA, pathology, filipin / oxysterol / 24(S)-HC / calbindin biomarkers; NIH-Vorinostat / Orphazyme-Arimoclomol / Vtesse-VTS-270 (HP-β-CD) pipeline; NPC-SS outcome measure; BALB/cNctr-Npc1m1N/-J KO mouse
TRPML1	1	TRPML1 / MCOLN1 ML-IV continuation, MK6-83 / ML-SA1 correction bullets, Libra / Calporta / Merck pipeline note, Tottori-univ-GD lipid + Olink + cytokine CSF / serum baseline-vs-post-Ambroxol matrix, CSF-GD-vs-Ctrl Olink p-value / Log2-FC table; Catecholamine pathway → levodopa pharmacology nav-vs-body drift at the bottom edge

For exact nav_path strings and headings see lysosome-autophagy and the matching by-nav indexes listed in related_topics_by_nav.

Across the 5 sources, source-note frontmatter records 22 uncertain_span_count entries and 0 body-embedded figure assets. The zero-figure-embed count reflects the 2026-04-29 body-purity decision (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md): the lysosome / autophagy pages carry the ⊞PhReT wide ion-transporter matrix, the Lysosomal changes in PD evidence-source table, the Plasma vs Blood analyte matrix, the Mizushima-2020 Assessment of lysosome mega-table with mixed assay-cell text, the LC3 / HSP70 chaperone-family cf table, the wide BMP BMP change in diseases matrix, the ETV:IDS (DNL310) brain-BMP-rescue Takeda slide pair (one mid-page and one bottom), the Type A / B / C Niemann-Pick comparison table with the NP-C symptoms-vs-age timeline schematic and the 2013 MolGenMetabo cerebellar-volume bar chart, the nested NPC pipeline sub- table, and the TRPML1 aSyn levels in PARK9 iPS model slide pair plus the Tottori-univ-GD Gantt-chart and Olink callout slides as mixed text+figure crops on the source pages — all kept as evidence rather than embedded. The 22 uncertain spans are retained as review targets and not resolved here.

Lysosomal Enzymes, Transporters, and Lysosomal Changes in PD

20240722_183416 anchors the chapter with the ⊞PhReT wide ion-transporter / TRPM1 (=MCOLN1) / TMEM175 / ATP13A2 matrix (function / LSD / LSD Ix? / LSD BM / Familial PD / sPD genetics / sPD pathology / Pt selection / Animal model columns), preceded by the bottom rows of an Ion transporters / PhReT wide multi-column table that continues from the previous photo (V-ATPase / P-ATPase / SLC family). Below the matrix a separate red / pink three-row Gene / In-vitro-phenotype-by-KO/KD / Improvement-by- O/E-or-activator table covers TMEM175, ATP13A2, TRPML1 with the references list (1)–(10). A target-disease relationship bullet block poses NPC / lipid-accumulation / MCOLN1 questions; a BMs block notes proteolytic / imaging / small-effect-size / pk/pd not possible / Comp-bio considerations and a KONDO AQB target-date question. The RD-DDU email from Y.H. Park (Metabolic Research Strategy Lead) records the Takeda DDU’s NPC / Evox exosome-therapy collaboration status, pharmacologic-futility / scale-up / manufacturing rationale for winding it down, and the tier-1 (Fabry / Gaucher / Pompe / MPSII / MPSIIIA / MLD) vs tier-2 (MPSI / MPSVI / NPC) DDU LSD priority list. A Lysosomal changes in PD source / sample / findings table follows (Chu 2009 postmortem SN, Carling 2020 fibroblast cohort, Anglade 1997 / Alvarez-Erviti 2010 thesis cite chain, Youn 2018 #643 early-PD ELISA cross-sectional rows; specific marker direction / cohort-size cells stay on the canonical page), and the Lysosomal Enzymes Cathepsin B / Cathepsin D enzyme table with substrate / Normally / arguments / Counterarguments columns including the cerezyme & ambroxol → cathepsin D correction note and the McGlinchey & Lee 2015 CTSB / CTSD aSyn-fibril-degradation reference. 5 Uncertain Spans. Carling-2020 / lysosomal-DEG genetics-side calls and ambroxol / cerezyme program-side application are delegated per the boundary table.

Assessment of Lysosome — Proteolysis / pH / Hydrolytic Activity Assays

20240722_183419 carries the tail of the lysosomal-enzyme summary table (Cathepsin C hardly detectable in CNS; Alpha-galactosidase Gb3 cross-references on Fabry mouse and PD-risk literature; neuraminidase row), the Plasma vs Blood analyte / sample-source matrix (GBA activity / BMP / GlcSph / Cathepsin D activity / LIMP2 across plasma / Fresh blood / PBMC / lymphocyte / CSF), and the Mizushima-2020-anchored Assessment of lysosome mega-table. The mega-table crosses category sub-rows ((global) / Proteolysis / (general) / Lysosomal pH / Lysosomal hydrolytic enzyme activity / (autophagic)) with technique columns (In vitro / Animal brain / Human brain / Human CSF / Mouse / Animal models) and reproduces, among others: Mazzulli 2011 GD iPS-neuron 3H- leucine pulse-chase, Henry 2015 #1174 mouse-primary-astrocytes 3H-valine 24 h pulse-chase, Jennings 2022 #2283 DNL201 AHA-labeling long-lived-protein quantification, Logan 2020 #1215 Denali Grn KO PTV:PGRN rescue (lysosomal proteolysis + BMP), DQ-Red BSA proteolysis assay, Gold-nanoparticle (AuNC) localisation, p62 / SQSTM1 autophagy reporter, LysoTracker / LysoSensor Yellow/Blue DND-160 / HCy-BIZ-BF2 NIR pH probes, magic-red Cathepsin B (with the Korean inline note (막상보니 in vitro 용이네) preserved verbatim), Cathepsin B & L per Nakanishi et al. 1994, Cathepsin D activity per Dottavio-Martin and Ravel 1978 / [125I]methemoglobin, Shi 2019 #1722 mouse body, Rocha 2015 #1253 mouse brain homogenate, Kurzawa 2012, Chu 2009 #266, and Youn 2018 #643 early-PD-patients ELISA. The Process sub-table at the bottom is the early-endosome / late-endosome / lysosome marker chain (RAB5A / RAB4 / Transferrin / EEA1 / RAB7 / RAB9 / mannose-6- phosphate receptors) cut at the bottom edge and continuing onto _183423. 4 Uncertain Spans. The page records Korean inline annotations across the assays block (proteolytic-marker caveats, gap-flagging asides, Cathepsin-activity questions); these stay on the canonical page rather than being re-quoted here. The DNL201 AHA-labeling and Denali PTV:PGRN rows are methodology-side referenced from the LRRK2 / pk-gt-pharmacology side per the boundary table.

Macroautophagy / Microautophagy / CMA / BMP

20240722_183423 is the canonical macroautophagy / microautophagy / CMA / BMP narrative page. The top of the page carries the lower portion of the endosome / MVB marker table that continues from _183419 (multi-vesicular endosomes vs MVB, fusion-with-plasma-membrane vs lysosome, exosome release). The Macroautophagy block opens with a resource callout pointing at the Novusbio LC3 FAQ and a paragraph summarising the LC3A / LC3B / LC3C family and the proLC3 → LC3-I → LC3-II maturation chain (Atg4 / Atg7 / Atg3 E2-like-enzyme cascade). Microautophagy is one sentence on direct-lysosome-membrane invagination. The CMA block records the HSC70 / KFERQ / LAMP2A canonical chain (Lynch-Day 2012, Cuervo 2004b), notes the disease-associated A30P / A53T aSyn cloggs the CMA translocation channels mechanism, and pairs CMA Pathology with the postmortem ↓ LAMP2A / ↓ HSC70 references (10–14). A Cf) HSP70- family table separates HSC70 (constitutive, Hsp73 / HSPA8) from HSP70 (stress-induced). The BMP (Bis(monoacylglycero)phosphate) block covers What-it-is / Presence / Function / BMP change in diseases (GBA-PD, LSDs, GD, GRN-FTD, In-vivo-brain rows; Alcalay 2020 #649, Akgoc 2015 #648, Hein 2013 #670, Denali PGRN_KSQ_Apr2020Update, Denali R&D-Day LRRK2-inhibitor → BMP note) and carries the ETV:IDS (DNL310) brain-BMP-rescue Takeda slide caption twice — once mid-page (body_r03) and once at the bottom (body_r05) — kept as evidence rather than embedded. The BMP Correction sub-block adds healthy- people Urine / CSF rows and an animal-model In-vivo-brain & CSF row (LRRK2-inhibitor → BMP correction). The page records a Korean meta- comment flagging that whether BMP is ↑ or ↓ in disease — and whether it is a cause or a consequence of lysosomal dysfunction — is itself uncertain (preserved verbatim on the canonical page), alongside a Takeda DMPK: BMP measurement ongoing GBA-PD CSF & plasma WIP note. 4 Uncertain Spans. The aSyn-CMA cloggs mechanism is delegated to alpha-synuclein; the GRN-FTD / PGRN row is delegated to inflammation; the Denali R&D-Day LRRK2-inhibitor → BMP-correction note is delegated to lrrk2; the ETV:IDS (DNL310) IDS-KO TfRmu/hu transcytosis vehicle is delegated to pk-gt-pharmacology and molecular-biology § GT Safety Appendix.

Niemann-Pick Disease — NPC1 / NPC2 Typing, Pipeline, Biomarkers

20240722_184247 is the Niemann-Pick disease wide-table chapter. Above the heading the page carries the tail of a Mucolipidosis-related Agreement / publication block (Anniversary year, C-BIG public dataset) that continues from _184233. The Type A / Type B / Type C comparison table runs across Cause / MIM / Inheritance / Onset / Life expectancy / Cause of death / Systemic Sx / Neurologic Sx / prevalence / Imaging / MOA / correction / PATHOLOGY / Dx / Tx / Pipeline / outcome measure / animal model / biomarker-established / biomarker-new rows; Type A and Type B columns are mostly empty while Type C is fully populated. Type C content includes the SMPD1 / NPC1 / NPC2 genetic basis, life-expectancy and cause-of-death notes (Dysphagia → aspiration pneumonia), the NP-C symptoms-vs-age timeline schematic kept as evidence, prevalence rows (J Rare Disease 2010 / NDDMF citations), the 2013 MolGenMetabo cerebellar-volume bar-chart (TCWM / TCGM / TCV NPC vs CTL) kept as evidence with surrounding MRI / NAA / choline narrative (Benussi 2018 review), the NPC1 / NPC2 LDL-cholesterol trafficking MOA, the correction bullet (Cao 2015 #1726 in vitro NPC1-/- ML-SA1 / mucolipin-1 O/E → ↓ lipofuscin; Miglustat; Cyclodextrin per whller 2019 preserved verbatim), the wheeler 2019 / zervas 2001 PATHOLOGY narrative (sphingolipid / cholesterol accumulation, Purkinje cell death, unesterified-cholesterol filipin staining), the filipin / oxysterol / Suspicion-Index Dx narrative, the Miglustat / Pineda 2018 review Tx note, the nested NIH-Vorinostat / Orphazyme-Arimoclomol / Vtesse- VTS-270 (HP-β-CD) Pipeline sub-table (NCT IDs, Phase, Enrollment, Study-Start, Estimated-Primary-Completion cells stay on the canonical page), the NPC-SS / 5-domain NPCCSS outcome measure, the BALB/cNctr-Npc1m1N/-J (NPC1 KO, NPC1NIH) mouse model row, the established-biomarker block (filipin staining, oxysterol, cholestane- triol; Elmonem 2020 #1715 review), and the new-biomarker block (Bradbury 2016 #1725 calbindin; Tortelli 2014 #1729; Porter 2010 #1730 plasma 24(S)-HC / cholestane-triol). 5 Uncertain Spans. Vorinostat / Arimoclomol / HP-β-CD / Miglustat program-side coverage and ML-SA1 / TRPML1-activator program rationale are delegated per the boundary table.

TRPML1 — Activators, Tottori GD Collaboration, Pipeline

20240722_184542 opens with the tail of an MCOLN1 / type-IV-mucolipidosis (ML-IV) paragraph continuing from the previous page (autophagosome-lysosome fusion role of MCOLN1 activation; LOF MCOLN1 → ML-IV; refs [143] / [144]). The Correction bullets record the TRPML1 activator MK6-83 → ↓ αSyn / ↓ lactosylceramide in PARK9 iPSC and mucolipidosis-type-IV models, and ML-SA1 → rescue of L-BMAA-induced motor-neuron death in an ALS model. The pipeline bullet covers Libra (TFEB-nuclear-translocation TE, overall expression unchanged; “in PD ↓ nuclear TFEB”; global protein degradation / macroautophagy / patient-stratification questions). The Tottori univ collaboration GD block carries a partial-text Calporta / Merck / Haoxing Xu / U-Michigan acquisition note (right column clipped at the photo’s left edge with parenthetic visual estimates preserved), an aSyn levels in PARK9 iPS model + Mucolipidosis type IV model slide pair (Cont 1 vs Mut 2 with DMSO / ML-SA1 / SF-22 treatments; Ca2+ channel dose-response; lactosylceramide bar chart) kept as evidence, a Gantt-chart PY2019 / PY2020 quarterly milestone slide and an Olink panel callout (Immuno-oncology / Inflammation / Neurology) kept as evidence, and the wide CSF / serum baseline-vs- post-Ambroxol matrix. The matrix strings together Lipid rows (GlcCer / GalSph / BMP / GlcSph) with Korean meta-commentary on dose- dependency / brain-vs-plasma-responsible GlcCer forms, an aSyn (MSD) Total-aSyn row with the “no correlation between CSF and serum-EV α-syn level” cell preserved, a long Olink proteomics block (Olink panel column In-Olink? / Our-분석? / Baseline / Post-Ambroxol-Tx response over progranulin / cathepsin S / L1 / D / B / Z / F / O / L2 / Procathepsin H / LAMP2 / LIMP2 (SCARB2) / Beclin / P62 / LC3 / heat-shock-protein rows), and a Cytokine (Olink) block with the Korean meta-aside on the encephalomyelitis-control caveat. A second wide table reproduces the CSF GD-vs-Ctrl Olink p-value / p-value- summary / FC (Log2) rows; specific FC and p-value cells stay on the canonical page. The TRPML1 page body drifts at the bottom edge into a Catecholamine pathway → levodopa pharmacology block (Tyrosine → Tyrosine-hydroxylase → L-Dopa → AADC → Dopamine → DBH → norepinephrine → PNMT → EPINEPHRINE reaction chain; VMAT note; Carbidopa / Sinemet / Benserazide / Madopar; Entacapone / Tolcapone / Opicapone / Stalevo; striatum levodopa initial-vs-maximum dosing range; Wearing-off mechanism bullet) that continues onto the next photo. The drift is preserved as recorded rather than reconciled; the page stays in sections/lysosome- autophagy by its TRPML1 nav root while the catecholamine / levodopa pharmacology body is delegated to clinical-pd. 4 Uncertain Spans. Tottori- univ-GD program-side coverage and the Ambroxol / GD-stratification biomarker matrix are delegated to ambroxol / gba-gcase-modalities / biomarkers-outcomes; the Olink-panel abbreviation row labels (EPM, FLM-1, DCP1, CSR1, CNU) are preserved as the photo records them.

Source Table

All 5 sources, in capture-time order, with the per-page uncertain-span and embedded-image counts copied verbatim from source-note quality_metrics. nav path is the full nav_path recorded in the source note (joined by >).

stem	nav path / heading	source note	canonical	uncertain spans	embedded images
20240722_183416	Lysosomal Enzymes	note	md	5	0
20240722_183419	RD-DDU > Lysosomal changes in PD > Lysosomal Enzymes > Assessment of lysosome > Marker	note	md	4	0
20240722_183423	Macroautophagy > Microautophagy > CMA > BMP (Bis(monoacylglycero…))	note	md	4	0
20240722_184247	Niemann-Pick disease	note	md	5	0
20240722_184542	TRPML1	note	md	4	0

Totals across the 5 sources: uncertain_span_count = 22, embedded_image_count = 0. These are review surface area; the zero-figure-embed count reflects the 2026-04-29 body-purity decision (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md) under which mixed text-and-figure crops on these pages are kept as evidence rather than embedded.

Uncertainties Carried Forward

This page does not paraphrase the ⊞PhReT wide ion-transporter / TMEM175 / ATP13A2 cells, the Lysosomal changes in PD source / sample / findings rows, the Cathepsin B / D arguments / Counterarguments cells, the Plasma vs Blood analyte rows, the Mizushima-2020 Assessment of lysosome mega-table cells, the LC3 / HSP70 chaperone-family cf table, the BMP change in diseases GBA-PD / LSDs / GD / GRN-FTD / In-vivo- brain rows, the ETV:IDS (DNL310) brain-BMP-rescue slide caption, the Type A / B / C Niemann-Pick comparison-table cells, the nested NPC pipeline sub-table cells, the BALB/cNctr-Npc1m1N/-J KO mouse row, the filipin / oxysterol / cholestane-triol / 24(S)-HC / calbindin biomarker cells, the TRPML1 Correction bullets, the Tottori-univ-GD CSF / serum matrix cells, the CSF GD-vs-Ctrl Olink p-value / Log2-FC table cells, or the bottom-edge catecholamine / levodopa pharmacology bullets. Specific uncertainty hot spots worth checking before any downstream extraction:

• ⊞PhReT and TMEM175 / ATP13A2 / TRPML1 KO/KD references — column boundaries inferred from the visible header row in a dense matrix; reference numbering rendered ambiguously ((#L,3) vs (#1,3), TMEM1175 vs TMEM175, Reference 4 PNAS year (2030) vs (2020)), and TRPM1 row (Ca2) subscript notation preserved as transcribed (20240722_183416, 5).
• Plasma-vs-Blood xicoy shorthand and the Mizushima-2020 Assessment of lysosome mega-table radiolabel / isotope cells ([3H]-valine, [125I]methemoglobin) — preserved as visible; the Process row marker list (RAB5A / RAB4 / Transferrin) is cut at the bottom edge and continues onto _183423 (20240722_183419, 4).
• BMP urine / CSF / brain rows — Korean fragment 다소 GBA+PD+LRRK2- vs GBA-PD+LRRK2- boolean qualifier (LRRK2- vs LRRK2+); the mu copolysaccharidosis token preserved as the source spells it; ETV:IDS slide group label IDS KO; TfRmu/hu micro-superscripts preserved; for 10 dyas dosing source typo preserved verbatim (20240722_183423, 4).
• Niemann-Pick Type-C cells — EPS, MR) closing-paren-without-opener preserved as printed (MR could be MRI truncated); Cao-2015 #1726 bullets use both figIe and fig6e (l vs I ambiguity); (whller 2019) preserved with its double-l typo; NP-C symptoms- vs-age schematic label Pediatric Spasmonotic preserved as visible (20240722_184247, 5).
• TRPML1 nav-vs-body drift on _184542: the TRPML1 nav-root page body drifts at the bottom edge into a Catecholamine pathway → levodopa-pharmacology block (Carbidopa / Sinemet / Madopar / Entacapone / Stalevo / Wearing-off) that continues onto the next photo; preserved as recorded, not reconciled. The Tottori-univ-GD Calporta / Merck / Haoxing Xu acquisition slide is clipped at the photo’s left edge with parenthetic visual estimates [gonist] / [ch] / [Michigan]; the CSF GD-vs-Ctrl Olink panel abbreviation row labels (EPM / FLM-1 / DCP1 / CSR1 / CNU) are preserved as recorded with their full-name mappings unconfirmed; the aSyn (MSD) row no correlation between CSF and serum-EV α-syn level is wrapped in a 4-column colspan because its visible scope is ambiguous (20240722_184542, 4).

Related Pages

• lysosome-autophagy — section index for all 5 sources
• gba-pd-biology — sibling topic; foundational GBA / GD / GBA-PD biology that consumes the Cathepsin D / cerezyme + ambroxol correction note and the BMP-GBA-PD row
• gba-gcase-modalities — sibling topic; GBA Activator / GBA GT / Substrate-pathway-correction modalities and the program-side application of the cathepsin / GlcCer / GlcSph / BMP biomarker vocabulary, including the Tottori-univ-GD CSF / serum baseline-vs-post-Ambroxol matrix
• ambroxol — owns the Ambroxol program; the Tottori univ collaboration GD post-Ambroxol-Tx CSF / serum matrix on _184542 and the cerezyme & ambroxol → cathepsin D correction note on _183416 are referenced from there
• eliglustat / venglustat / pr001 — own the Substrate-pathway-correction program rows that the cathepsin / GlcCer / GlcSph / BMP biomarker rows feed
• alpha-synuclein — sibling topic (Tier 1); owns the aSyn KFERQ / LAMP2A / HSC70 CMA biology, A30P / A53T cloggs mechanism, CTSB / CTSD aSyn-fibril degradation, and aSyn-levels-in-PARK9-iPSC TRPML1-activator rescue context
• parkin / parkn-gt — own mitophagy / PINK1 / pS65-Ub / Parkin-mediated autophagosome wrapping that the macroautophagy LC3 vocabulary on _183423 underwrites
• mitochondria — sibling topic; owns MAM / Complex I / mitophagy / 31P MRS disease-side coverage that re-uses the lysosomal-autophagy vocabulary
• inflammation / nlrp3-inhibitor — own microglia / TNFα / NLRP3 / Complement / pyroptosis biology and the Denali PGRN_KSQ_Apr2020Update GRN-FTD CSF BMP row context
• lrrk2 — sibling section for the LRRK2 pipeline (4 sources, including DNL151 / DNL201); the Jennings 2022 #2283 DNL201 AHA labeling long-lived-protein assay on _183419 and the Denali R&D-Day LRRK2-inhibitor → ↓ BMP correction note on _183423 are referenced from there
• pk-gt-pharmacology / molecular-biology — sibling topics; AAV / capsid / promoter / route-of-administration / FDA-CTGT-2021 GT-safety vocabulary that the Niemann-Pick / TRPML1 pipeline rows imply, and the ETV:IDS (DNL310) IDS-KO TfRmu/hu transcytosis vehicle on _183423
• genetics-pathway — sibling topic; Carling-2020 lysosomal-dysfunctional DEG VarElect / KEGG calls (CTSD, SMPD1, NPC1, …), variant-pathogenicity / ACMG-AMP-style criteria framework, and HGVS / Genotyping methodology that GBA1 / NPC1 / NPC2 calls would consume
• biomarkers-outcomes — sibling topic; [BIOMARKER] validation / qualification framework, plasma-vs-blood / serum / CSF analyte-selection criteria, NfL / synaptic-change biology that the Cathepsin / BMP / LIMP2 / GlcSph biomarker rows on _183419 and _184542 would feed
• bioorchestra-biomarker-catalog — sibling topic; the BioOrchestra _182708–_183115 chain re-uses cathepsin / BMP / LAMP2 / LIMP2 analyte vocabulary
• msa / msa — sibling topic / section; MSA-side aSyn / autophagy / lysosomal coverage that mirrors the macroautophagy / CMA vocabulary
• clinical-pd — sibling topic; Catecholamine pathway → levodopa / Carbidopa / Sinemet / Madopar / Entacapone / Stalevo / Wearing-off pharmacology continuation from the bottom edge of _184542
• therapeutic-programs — program-routing map; Vorinostat / Arimoclomol / HP-β-CD / Miglustat / Cyclodextrin / TRPML1-activator (MK6-83, ML-SA1) / Calporta-Merck NPC1 / TRPML1 program-side rows are not promoted to entity pages in v1 and remain Entity Backlog Candidates here
• operations — sibling section; RD-DDU NPC / Evox correspondence with Y.H. Park’s tier-1 / tier-2 LSD priority list and DDU resourcing strategy on _183416 belong to the Operations / RD-program governance axis
• lysosomal-enzymes — Lysosomal Enzymes first-nav_path index
• rd-ddu — RD-DDU first-nav_path index
• macroautophagy — Macroautophagy first-nav_path index
• niemann-pick-disease — Niemann-Pick disease first-nav_path index
• trpml1 — TRPML1 first-nav_path index
• source-catalog — all 447 sources in capture order
• nav-path-index — 376 distinct nav_paths