Lysosomal acid lipase (LAL) (LIPA)

Lysosomal acid lipase (LAL), encoded by the LIPA gene, is a critical enzyme responsible for the hydrolysis of cholesteryl esters and triglycerides within the lysosomal compartment of cells (UniProt P38571). This process is essential for the regulation of intracellular lipid levels and the maintenance of cholesterol homeostasis (NCBI Gene ID: 3988). When LAL activity is deficient due to mutations in the LIPA gene, it leads to the accumulation of lipids in various tissues, particularly the liver, spleen, and blood vessel walls (StatPearls: Lysosomal Acid Lipase Deficiency). This deficiency manifests clinically as Lysosomal Acid Lipase Deficiency (LAL-D), which includes the severe, early-onset Wolman disease and the later-onset Cholesteryl ester storage disease (CESD) (NORD: Lysosomal Acid Lipase Deficiency). Therapeutic intervention primarily involves enzyme replacement therapy with Sebelipase alfa, which aims to restore enzymatic activity and reduce systemic lipid accumulation (FDA: Kanuma Approval). Monitoring treatment efficacy typically involves measuring liver enzymes and lipid profiles, as well as assessing organ volume (PubMed: PMC4640154).

Other names

Acid cholesteryl ester hydrolaseCholesterol esteraseLysosomal acid lipase/cholesteryl ester hydrolaseLAL

Sebelipase alfa is a recombinant human lysosomal acid lipase that binds to mannose receptors on the surface of target cells, leading to its internalization and trafficking to the lysosome, where it replaces the missing endogenous enzyme to hydrolyze accumulated lipids (FDA Label: Kanuma).