Angiopoietin-like protein 3 (ANGPTL3), also known as Angiopoietin-related protein 3 or Angiopoietin-5 (ANGPT5/ANG-5), is a member of the angiopoietin-like family of secreted factors. ANGPTL3/ANGPT5 is predominantly expressed in the liver and has the characteristic structure of angiopoietins, including a signal peptide, an N-terminal coiled-coil domain, and a C-terminal fibrinogen (FBN)-like domain. The FBN-like domain of ANGPTL3 has been shown to bind to alpha-5/beta-3 integrins, inducing endothelial cell adhesion and migration. This protein may also play a role in the regulation of angiogenesis.
ANGPTL3 acts as a dual inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), increasing plasma triglyceride and HDL cholesterol levels in rodents. By inhibiting endothelial lipase, ANGPTL3 prevents the catalysis of HDL-phospholipid, thereby increasing HDL-phospholipid (HDL-PL) levels. Circulating phospholipid-rich HDL particles have high cholesterol efflux capabilities.