A protein of capillary endothelial cells, GPIHBP1, is crucial for plasma triglyceride metabolism

The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is crucial for delivering dietary lipids to tissues. For years, the mechanism by which LPL (which is secreted by myocytes and adipocytes) reaches its site of action within blood vessels was mysterious. We discovered that GPIHBP1, a protein of capillary endothelial cells, captures LPL within the interstitial spaces and shuttles it to the luminal surface of capillaries. GPIHBP1's three-fingered LU (Ly6/uPAR) domain binds stably to LPL's C-terminal domain. An intrinsically disordered acidic domain in GPIHBP1 accelerates the kinetics of LPL binding, stabilizes the conformational integrity of LPL's N-terminal hydrolase domain (thereby preserving LPL activity), and plays a critical role in the transport of LPL to the capillary lumen.