Lysosomal Acid Lipase (LIPA), also known as lysosomal acid lipase/cholesteryl ester hydrolase (LIPA/CEH), is an essential hydrolase enzyme responsible for the hydrolysis of cholesteryl esters and triglycerides within lysosomes. The enzyme plays a critical role in lipid metabolism, breaking down lipoprotein-derived lipids for cellular use. This 374-amino acid enzyme is particularly important in [neurons](/entities/neurons), where lipid homeostasis is crucial for membrane maintenance, synaptic function, and myelin integrity.
Lysosomal Acid Lipase (LIPA), also known as lysosomal acid lipase/cholesteryl ester hydrolase (LIPA/CEH), is an essential hydrolase enzyme responsible for the hydrolysis of cholesteryl esters and triglycerides within lysosomes. The enzyme plays a critical role in lipid metabolism, breaking down lipoprotein-derived lipids for cellular use. This 374-amino acid enzyme is particularly important in [neurons](/entities/neurons), where lipid homeostasis is crucial for membrane maintenance, synaptic function, and myelin integrity.
Mutations in the LIPA gene cause lysosomal storage disease (LSD) called lysosomal acid lipase deficiency (LALD/Wolman disease when severe, and CESD when partial), highlighting the enzyme's essential role in cellular lipid processing. Recent research has implicated LIPA dysfunction in neurodegenerative diseases, particularly Parkinson's disease.[@grabowski2008]
Protein Name: LIPA - Lysosomal Acid Lipase
UniProt ID: P38571
Gene: [LIPA](/genes/lipa)
Molecular Weight: ~43 kDa (374 amino acids)
Protein Class: Hydrolase, Lysosomal enzyme
Tissue Expression: High in liver, adrenal glands, small intestine, brain
Subcellular Localization: Lysosome
Molecular Structure
LIPA is synthesized as a precursor that undergoes processing:
Signal peptide: Targets the protein to the secretory pathway
Propeptide: Cleaved in the Golgi to form mature enzyme
Active site: Ser-Asp-His catalytic triad
N-linked glycosylation: Essential for proper folding and stability
The enzyme has a classic α/β hydrolase fold with a lid domain that regulates substrate access. The active site contains a nucleophilic serine, which is essential for catalysis.[@lohse2010]
Function
LIPA performs essential functions in cellular lipid metabolism:
Cholesteryl ester hydrolysis: Converts cholesteryl esters to free cholesterol and fatty acids
Triglyceride hydrolysis: Processes triglycerides from internalized lipoproteins
Lysosomal lipid catabolism: Essential for the final step of lipoprotein processing
Cholesterol homeostasis: Releases cholesterol for cellular use and efflux
[Autophagy](/entities/autophagy)-lipophagy: Involved in lipid droplet degradation through lipophagy
The enzyme works optimally at acidic pH (4.5-5.0), characteristic of lysosomal environment. It can hydrolyze both cholesteryl esters and triglycerides, though with different efficiencies.[@rinella2013]
Role in Neurodegeneration
Parkinson Disease
Lipid metabolism: LIPA variants associated with PD risk