LPL

LPL Full Name

lipoprotein lipase

LPL Introduction

Lipoprotein lipase (LPL) is a secreted enzyme primarily expressed in adipose tissue, skeletal muscle, cardiac muscle, and the lactating mammary gland, where it plays an essential role in lipid transport and energy homeostasis. It is anchored to the endothelial surface of capillaries through interactions with glycosylphosphatidylinositol-anchored high-density lipoprotein–binding protein 1 (GPIHBP1), which facilitates the capture and processing of circulating triglyceride-rich lipoproteins. Structurally, LPL contains a catalytic domain with a classic serine hydrolase motif and a heparin-binding domain that helps localize the enzyme to the endothelium. Its activity is tightly regulated by hormones, nutritional status, and lipid-sensing proteins such as angiopoietin-like proteins (ANGPTLs).

Figure 1. Regulatory processes that influence cardiac lipoprotein lipase action and the utilization of delivered FAs.(Source: Shang R, et al.; 2021)

Functionally, LPL hydrolyzes the triglycerides carried in chylomicrons and very low-density lipoproteins (VLDL), releasing free fatty acids and monoacylglycerols that can be taken up by nearby tissues for storage or energy production. Through this process, LPL controls the metabolic partitioning of lipids and influences whole-body insulin sensitivity, thermogenesis, and lipoprotein remodeling. LPL also plays a vital role in generating remnant lipoproteins that are subsequently cleared by the liver, and its enzymatic activity is essential for maintaining normal plasma triglyceride levels. Beyond lipid hydrolysis, LPL participates in signaling functions by modulating the interaction of lipoproteins with cell-surface receptors and contributing to the trafficking of lipid-derived signaling molecules.

Genetic or functional defects in LPL are strongly associated with metabolic diseases. Loss-of-function mutations lead to familial chylomicronemia syndrome (FCS), a rare condition characterized by extreme hypertriglyceridemia, recurrent pancreatitis, eruptive xanthomas, and hepatosplenomegaly. Partial deficiencies or dysregulation of LPL activity contribute to common disorders such as metabolic syndrome, type 2 diabetes, obesity, and cardiovascular disease, where impaired triglyceride clearance exacerbates atherogenic lipoprotein profiles. Conversely, increased LPL activity in adipose tissue may promote lipid accumulation and weight gain. Because of its central role in lipid metabolism, LPL is a therapeutic target in drug development aimed at lowering triglycerides, improving insulin sensitivity, and reducing cardiovascular risk, with emerging strategies including gene therapy, antisense oligonucleotides, and modulators of ANGPTLs and GPIHBP1.

Alternate Names for LPL

LPL; lipoprotein lipase; LIPD; HDLCQ11;

• 1.Shang R, Rodrigues B. Lipoprotein Lipase and Its Delivery of Fatty Acids to the Heart. Biomolecules. 2021, 11(7):1016.