LAMP1 review notes

Core function

LAMP1 encodes a heavily glycosylated type I lysosomal membrane glycoprotein.
UniProt describes the protein as a lysosome, endosome, late endosome, cell
membrane, and cytolytic granule membrane protein that shuttles through the
endolysosomal/secretory-lysosome system [file:human/LAMP1/LAMP1-uniprot.txt].
The most informative current molecular function is regulation of lysosomal pH:
LAMP1 and LAMP2 directly interact with TMEM175 and inhibit TMEM175 cation/proton
channel activity, which facilitates lysosomal acidification and hydrolase
activity PMID:37390818.

The core GO interpretation should therefore keep GO:0005765 lysosomal membrane
as the primary location, accept GO:0007042 lysosomal lumen acidification, and
accept GO:0008200 ion channel inhibitor activity as the best available broad
MF term for the TMEM175 inhibition mechanism. The local GO cache does not contain
a more specific proton-channel or TMEM175-channel inhibitor term.

Proteostasis network context

The Proteostasis Network places LAMP1 under
Autophagy-Lysosome Pathway|Autophagic lysosome reformation|Regulation of autolysosome morphology.
The node is marked no_mapping, so PN membership alone is not evidence for a GO
annotation. The workbook note says LAMP1 recruits clathrin to tubules during ALR,
but the locally cached Rong et al. ALR abstract supports clathrin and PI(4,5)P2
as central ALR components without providing a LAMP1-specific statement
PMID:22885770.
I am therefore not adding a new ALR/lysosome-organization annotation from the PN
row alone. Expert follow-up should ask whether the LAMP1-specific clathrin
recruitment evidence is in figures or supplemental material that should support
a future annotation.

Secondary functions and contexts

LAMP1 has a non-core but well-supported role in cytotoxic lymphocyte secretory
lysosomes. LAMP1 RNAi in NK cells reduces cytotoxicity, disturbs lytic-granule
movement, and reduces perforin delivery to lytic granules PMID:23632890. Surface LAMP1 also
protects NK cells from degranulation-associated self-damage by reducing perforin
binding PMID:23847195.
These support NK-cell and cytolytic-granule annotations, but they are not the
general core function of LAMP1.

LAMP1 also stabilizes the lysosomal polypeptide transporter TAPL/ABCB9. The TAPL
paper reports LAMP1/LAMP2 as abundant TAPL interactors and shows that TAPL
half-life is reduced in LAMP-deficient cells PMID:22641697.
This supports protein stabilization as a secondary process, while generic
enzyme/protein-binding annotations are not informative.

LAMP1 is a host factor/receptor for Lassa virus entry in acidic endolysosomal
compartments; this is a valid host-pathogen context but not a normal human core
function PMID:24970085.

Annotation decisions

• Accept lysosomal membrane, endosome membrane, and late endosome membrane as the
  core membrane locations; modify broader lysosome/endosome/membrane terms to
  those more specific membrane terms.
• Keep plasma membrane, cell surface, cytolytic granule membrane, azurophil
  granule membrane, ficolin-1-rich granule membrane, extracellular exosome, and
  other trafficking/localization terms as non-core contexts.
• Remove cytosol/cytoplasm annotations because LAMP1 is an integral membrane
  protein; the cytosolic tail does not justify annotating the whole protein to
  cytosol.
• Accept lysosomal lumen acidification and ion channel inhibitor activity as core
  TMEM175-dependent functions.
• Modify broad protein binding to more informative terms where possible:
  TMEM175 binding to ion channel inhibitor activity, Lassa virus binding to virus
  receptor activity, and ABCB9/TAPL binding to protein stabilization.
• Keep NK-cell degranulation/cytotoxicity and perforin transport terms as
  non-core, cell-type-specific functions.

Deep research provenance

Falcon deep research was started with just deep-research-falcon human LAMP1.
The provider timed out after 600 seconds and no LAMP1-deep-research-falcon.md
file was generated in the gene folder. This review therefore relies on cached
GOA/UniProt, cached publications, PN mappings, and these notes.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

• Moved out of the YAML description: existing GOA correctly captures lysosomal membrane, late endosome membrane, lysosomal lumen acidification, and broad ion channel inhibitor activity; broad lysosome, endosome, membrane, and generic binding annotations should be narrowed; NK-cell cytotoxicity, TAPL/ABCB9 stabilization, Lassa virus receptor activity, plasma membrane exposure, and lysosome-related granule locations are secondary contexts. The Proteostasis Network ALR morphology row is useful search context but does not by itself justify a new ALR annotation for LAMP1.