Angiopoietin-like 3 (ANGPTL3) is a secreted glycoprotein that is structurally related to the angiopoietins. Mature human ANGPTL3 contains an N-terminal coiled coil domain and a C-terminal fibrinogen-like domain. ANGPTL3 is expressed in the liver from early in development through adulthood. Full length ANGPTL3 circulates in the plasma as do the proteolytically separated N-and C-terminal segments containing the coiled coil domain and fibrinogen-like domains,respectively. ANGPTL3 directly inhibits lipoprotein lipase (LPL) and endothelial lipase (EL), enzymes responsible for hydrolyzing circulating triglycerides and HDL phospholipids. ANGPTL3 promotes an increase in circulating triglyceride levels without altering VLDL or HDL secretion or uptake. ANGPTL3 expression in vivo is up-regulated by LXR agonists and down-regulated by insulin, leptin, and agonists of TRβ or PPARβ.