Lipase A, lysosomal acid type

Lipase A, lysosomal acid type is a protein that in humans is encoded by the LIPA gene.

Function

This gene encodes lipase A, the lysosomal acid lipase. This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides, leading to the production of free cholesterol and fatty acids. Notably, LAL is the only known acid lipase that hydrolyzes cholesteryl esters and triglycerides within the lysosomal environment.
LAL is essential to intracellular lipid metabolism in macrophages and hepatocytes. Upon uptake of LDL by endocytosis, cholesteryl esters and triglycerides are transported to lysosomes where they are hydrolyzed by LAL. The resulting free cholesterol either exits the lysosome for future use in membrane synthesis or is re-esterified in the endoplasmic reticulum by ACAT to form lipid droplets. This process is important for foam cell formation during atherogenesis.
The importance of LAL in cardiovascular disease has been highlighted by GWAS studies, which have identified variants in the LIPA locus that are associated with coronary artery disease. LAL was found to have high expression in macrophages located in atherosclerotic plaques, where its activity contributes to the accumulation of lipid droplets and the progression of plaque development.
Mutations in the LIPA gene that cause loss-of-function can result in infant-onset Wolman disease, caused by a complete lack of LAL production, or a later-onset Cholesterol ester storage disease, caused by a 5-10% reduction in LAL production.
Alternatively spliced transcript variants have been found for this gene. .