Angiopoietin-like protein 4 (ANGPTL4) (ANGPTL4)

Angiopoietin-like protein 4 (ANGPTL4) is a secreted glycoprotein that functions as a potent inhibitor of lipoprotein lipase (LPL), the primary enzyme responsible for the hydrolysis of triglycerides in the circulation (UniProt Q9BY76). By regulating LPL activity, ANGPTL4 serves as a major gatekeeper of lipid distribution and plasma triglyceride levels, particularly during fasting or stress (Kersten, 2021). Genetic studies have demonstrated that loss-of-function variants in the ANGPTL4 gene are associated with significantly lower triglyceride levels and a reduced risk of coronary artery disease (Dewey et al., 2016). Beyond metabolism, ANGPTL4 is involved in modulating angiogenesis, vascular permeability, and inflammation, and its expression is often upregulated in various cancers to facilitate metastasis. While it represents a promising therapeutic target for dyslipidemia, the development of ANGPTL4 inhibitors has been complicated by safety observations in animal models, specifically mesenteric lymphadenopathy and lipid malabsorption. Current research continues to explore the balance between its metabolic benefits and potential systemic side effects.

Other names

Fasting-induced adipose factorFIAFPPARG angiopoietin-related proteinPGARHepatic fibrinogen/angiopoietin-related proteinHFARPAngiopoietin-related protein 4NL2

Inhibition of ANGPTL4 prevents the reversible inactivation of lipoprotein lipase (LPL), thereby increasing the hydrolysis of triglycerides in chylomicrons and very-low-density lipoproteins (VLDL) (Kersten, 2021).