LIPA (lysosomal acid lipase) review notes

UniProt P38571 (LICH_HUMAN), HGNC:6617. Falcon deep research was launched for this gene but failed;
the synthesis below was done manually from the cached publications, the Reactome entries
and the UniProt record.

Core biology

• LIPA encodes lysosomal acid lipase / cholesteryl ester hydrolase (LAL, EC 3.1.1.13), the
  only lysosomal enzyme hydrolyzing cholesteryl esters and triacylglycerols delivered to
  lysosomes by endocytosis of LDL
  PMID:1718995.
• Purified human liver LAL hydrolyzes trioleoylglycerol, cholesteryl oleate and 1,2-/1,3-
  dioleoylglycerols; TAG and CE hydrolytic activities co-purify
  PMID:7204383.
• Acid pH optimum, consistent with lysosomal action
  PMID:8112342.
• LAL is synthesized as a preproprotein; the pro-region is required for folding and activity
  PMID:15269241.

Disease

• Biallelic LIPA variants cause lysosomal acid lipase deficiency: infantile-onset (Wolman
  disease) and childhood/adult-onset (CESD)
  PMID:26225414.
• Residual activity tracks severity
  PMID:9633819.
• dismech Wolman_Disease marks GO:0004771 sterol ester esterase activity and GO:0004806
  triacylglycerol lipase activity DECREASED in the lysosomal lumen, with GO:0046461 and
  GO:0019433 DECREASED: consistent with the core functions below.

Annotation decisions (summary)

• Core: sterol ester esterase activity (GO:0004771), triacylglycerol lipase activity
  (GO:0004806), lysosome/lysosomal lumen.
• General IEA parent MF terms (lipase activity, hydrolase acting on ester bonds, carboxylic
  ester hydrolase) modified to the specific activities.
• Core BP in core_functions: GO:0046461 neutral lipid catabolic process and GO:0090122
  cholesterol ester hydrolysis involved in cholesterol transport (defined as lysosomal
  cholesterol ester hydrolysis that feeds intracellular cholesterol transport; currently
  annotated in GOA only to CES1 by TAS). Not entered as NEW existing_annotations.