## ATP6V1E2
- **UniProt:** Q96A05 · **batch:** proteostasis-batch-2026-06-07 · **review status:** COMPLETE
- **PN placement:** two ALP leaves "V1 lysosomal v-ATPase proton pump component" (Nutrient sensing; Lysosomal acidification). **PN-node mapping:** leaf→GO:0046612 lysosomal V1 domain (more_specific_than_existing_goa); leaf→GO:0033176 V-type ATPase complex (new_to_goa); type→GO:0007042 lysosomal lumen acidification (new_to_goa).
- **Consistency:** CONFLICT on compartment. Review/notes establish E2 as the testis/sperm-enriched subunit-E paralog forming EG peripheral stalks; its plausible specialized compartment is the **acrosome** (acrosomal vesicle, GO:0001669, KEEP_AS_NON_CORE, orthology IEA) — a lysosome-related organelle, not the lysosome. The review carries no lysosomal annotation and MARKs_AS_OVER_ANNOTATED the macroautophagy NAS and five bare protein-binding IPIs. PN places E2 under "lysosomal v-ATPase" and projects lysosomal lumen acidification — mismatched to the sperm/acrosome biology. PN Notes template ("pumps protons into the lysosome") mis-frames this isoform.
- **PN story / NEW pressure:** PN's lysosomal lumen acidification (new_to_goa) OVER-REACHES for E2. GO:0046612/GO:0007042 verified real but wrong specialization; the evidenced organelle is acrosome (lysosome-related, not lysosome). E2 lacks direct human localization evidence at all (acrosome is IEA-only). **Lysosomal projection should NOT be propagated; if anything, an acrosome/lysosome-related-organelle framing is the honest one, but evidence is orthology-only.**
- **Mapping strategy:** Like B1/G3, E2 is a tissue-restricted isoform whose specialized compartment is not the lysosome (TOMM20/HSPA8/RAB7A "too broad" precedent applies). **[MAP]** flag E2 as an exception to lysosomal projection; safe target is the generic catalytic/V1 complex term (GO:0033178, already in review). Acrosome remains non-core/IEA.
- **Evidence alignment:** No overlap. PN cites generic reviews; review cites E2-specific PMID:12036578 (testis-specific isoform) plus high-throughput interactome PMIDs (all over-annotated). Review better-targeted to the gene.
- **Verdict:** OVER-REACH — PN lysosomal projection wrong-compartment for this testis/acrosome isoform (and acrosome itself is IEA-only). **Recommended edits:** [MAP] exempt ATP6V1E2 from lysosomal-acidification/lysosomal-V1 projection; restrict to vacuolar/catalytic V1 complex terms; keep acrosome as non-core.