LPL

Lipoprotein lipase (LPL), also termed LIPD or hepatic triglyceride lipase, is a glycoprotein enzyme anchored to vascular endothelial surfaces via heparan sulfate proteoglycans. It catalyzes the hydrolysis of triglyceride-rich lipoproteins (chylomicrons and VLDL) into free fatty acids and glycerol, facilitating lipid storage in adipose tissue and energy delivery to muscles. LPL activity is regulated by apolipoproteins (e.g., APOC2 as activator, APOA5 as stabilizer) and modulated by insulin, angiopoietin-like proteins (ANGPTL3/4/8), and PPAR signaling pathways. Genetic LPL deficiency causes familial chylomicronemia syndrome (Type I hyperlipoproteinemia), characterized by severe hypertriglyceridemia and pancreatitis. Conversely, LPL dysfunction is implicated in atherosclerosis, diabetes, and obesity. Therapeutic strategies include volanesorsen (APOC3 antisense oligonucleotide) for familial chylomicronemia and investigational gene therapies targeting LPL mutations. Small-molecule LPL activators and ANGPTL3/4 inhibitors are under preclinical evaluation for cardiometabolic disorders.