ANGPTL4 inactivates lipoprotein lipase by catalyzing the irreversible unfolding of LPL's hydrolase domain

The ANGPTL proteins regulate the catalytic activity of lipoprotein lipase (LPL) by catalyzing the unfolding of LPL's N-terminal hydrolase domain. Intravascular processing of triglyceride-rich lipoproteins depends on LPL and GPIHBP1 (an endothelial cell protein that binds LPL and transports it to the capillary lumen). A deficiency of either protein severely impairs triglyceride hydrolysis, resulting in markedly elevated plasma triglyceride levels and a substantial risk of acute pancreatitis. Angiopoietin-like proteins (ANGPTL) 3, 4, and 8 regulate LPL activity.