LPL Gene (Lipoprotein Lipase): Function, Mutations & Disease Associations

The LPL gene encodes lipoprotein lipase, a rate-limiting enzyme in the hydrolysis of triglycerides from circulating chylomicrons and very low-density lipoproteins (VLDL). This enzyme is primarily expressed in adipose tissue, skeletal muscle, and cardiac muscle, where it facilitates the release of free fatty acids for energy production or storage. Defects in the LPL gene are the primary cause of familial chylomicronemia syndrome (Type I hyperlipoproteinemia), characterized by severe hypertriglyceridemia and recurrent pancreatitis. The protein functions as a homodimer and requires glycosylation and the cofactor apolipoprotein C-II for optimal activity.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Triglyceride Metabolism

• Lipoprotein Metabolism

• PPAR Signaling Pathway

• Fatty Acid Degradation

Lipoprotein lipase (LPL) is a secreted glycoprotein that functions as a homodimer. It is the principal enzyme responsible for the hydrolysis of triglycerides in plasma lipoproteins, primarily chylomicrons and very low-density lipoproteins (VLDL). The enzyme is anchored to the luminal surface of capillary endothelial cells via glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1). LPL activity is crucial for providing free fatty acids to peripheral tissues for energy production or storage. Its activity is regulated by nutritional status, hormones, and the cofactor apolipoprotein C-II. Deficiency or dysfunction of LPL leads to severe hypertriglyceridemia and associated clinical complications.