Lipoprotein lipase and lysosomal lipolytic enzymes (LPL and LAL)

Lipoprotein lipase (LPL) and lysosomal lipolytic enzymes, primarily lysosomal acid lipase (LAL), are essential hydrolases that regulate lipid homeostasis by breaking down triglycerides and cholesteryl esters [1, 2]. LPL is anchored to the vascular endothelium and is responsible for the hydrolysis of triglycerides in circulating chylomicrons and very-low-density lipoproteins (VLDL), facilitating fatty acid uptake by tissues [1, 3]. LAL, conversely, functions within the acidic environment of lysosomes to degrade lipids internalized via receptor-mediated endocytosis, a process vital for cellular cholesterol regulation [2, 4]. Deficiencies in these enzymes lead to severe metabolic pathologies: LPL deficiency causes extreme hypertriglyceridemia and recurrent pancreatitis, while LAL deficiency (Wolman disease or cholesteryl ester storage disease) leads to multi-organ lipid accumulation and liver failure [1, 2]. Pharmacological management includes fibrates to induce LPL activity, biologics like volanesorsen to inhibit LPL suppressors, and sebelipase alfa as an enzyme replacement for LAL [3, 4, 5]. These targets are central to treating both common dyslipidemias and rare genetic lipid storage disorders.

Other names

LPLLALLIPALysosomal acid lipaseTriacylglycerol lipaseLipoprotein lipase deficiency protein

Activation of lipoprotein lipase (LPL) via PPAR-alpha agonism or reduction of inhibitors like ApoC-III/ANGPTL3 to increase triglyceride clearance; enzyme replacement therapy for lysosomal acid lipase (LAL) to restore lysosomal lipid degradation.