Angiopoietin-like 4 (ANGPTL4) is a multifaceted protein that belongs to the angiopoietin-like protein family. One of the primary functions of ANGPTL4 is to govern fatty acid delivery to cells by inhibiting lipoprotein lipase (LPL) activity. Overexpression of ANGPTL4 in mice leads to hypertriglyceridemia, while deficiency reduces circulating lipids and lowers the risk of coronary artery disease in humans. ANGPTL4 is highly expressed in adipose tissues and liver, where it primarily regulates lipid metabolism. In addition to its metabolic roles, ANGPTL4 is also expressed in vascular endothelium and has been reported to regulate endothelial cell functions such as vascular inflammation, nitric oxide production, angiogenesis, and vascular permeability. ANGPTL4 has been identified as a central player in energy homeostasis, at least in part, through its inhibitory interaction with LPL. The fibrinogen-like domain of ANGPTL4 interacts and activates specific integrins, which facilitate wound healing, modulate vascular permeability, and regulate reactive oxygen species (ROS) levels to promote tumorigenesis.
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