GPIHBP1 and the processing of triglyceride-rich lipoproteins

GPIHBP1 is a new addition to a group of proteins required for the lipolysis of triglyceride-rich lipoproteins. GPIHBP1 contains an acidic domain and an Ly6 domain with ten cysteines. GPIHBP1 binds lipoprotein lipase avidly and probably tethers lipoprotein lipase to the luminal surface of capillaries. Inactivation of Gpihbp1 in mice is associated with milky plasma and severe chylonnicronemia, even on a low-fat chow diet. Recently, four missense mutations in GPIHBP1 were identified in humans with severe chylomicronemia (C65Y, C65S, C68G and QII5P). All four mutations involve highly conserved residues within GPIHBP1's Ly6 domain. This article provides an update on GPIHBP1's role in the processing of chylomicrons and the pathogenesis of chylomicronemia.