GPIHBP1 acts as an endothelial cell transporter for lipoprotein lipase, and mutations in either GPIHBP1 or LPL that disrupt their interaction cause severe hypertriglyceridemia (chylomicronemia).
This review highlights the critical role of GPIHBP1 as an endothelial transporter for lipoprotein lipase and its genetic implications in severe hypertriglyceridemia.
Interest in lipolysis and the metabolism of triglyceride-rich lipoproteins was recently reignited by the discovery of severe hypertriglyceridemia (chylomicronemia) in glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1)-deficient mice. GPIHBP1 is expressed exclusively in capillary endothelial cells and binds lipoprotein lipase (LPL) avidly. These findings prompted speculation that GPIHBP1 serves as a binding site for LPL in the capillary lumen, creating "a platform for lipolysis." More recent studies have identified a second and more intriguing role for GPIHBP1-picking up LPL in the subendothelial spaces and transporting it across endothelial cells to the capillary lumen. Here, we review the studies that revealed that GPIHBP1 is the LPL transporter and discuss which amino acid sequences are required for GPIHBP1-LPL interactions. We also discuss the human genetics of LPL transport, focusing on cases of chylomicronemia caused by GPIHBP1 mutations that abolish GPIHBP1's ability to bind LPL, and LPL mutations that prevent LPL binding to GPIHBP1.
Young et al. (Tue,) conducted a review in Severe hypertriglyceridemia (chylomicronemia). GPIHBP1 mutations was evaluated. GPIHBP1 acts as an endothelial cell transporter for lipoprotein lipase, and mutations in either GPIHBP1 or LPL that disrupt their interaction cause severe hypertriglyceridemia (chylomicronemia).