Angiopoietin-like protein 4 (ANGPTL4)

Angiopoietin-like protein 4 (ANGPTL4) is a secreted glycoprotein encoded by the *ANGPTL4* gene and is a member of the angiopoietin-like family. It is highly expressed in adipose tissue and liver but is found in multiple tissues and secreted into circulation. ANGPTL4 is upregulated in response to hypoxia and by peroxisome proliferator-activated receptors (PPARs). It plays a central role in the regulation of lipid and glucose metabolism—primarily through inhibition of lipoprotein lipase (LPL), thus controlling plasma triglyceride levels and influencing glucose homeostasis. ANGPTL4 is involved in the modulation of vascular permeability, angiogenesis, and inflammatory responses, and is a key factor in the pathogenesis of several diseases, including various cancers (where it can promote tumor growth, invasion, metastasis, and resistance to therapy), proliferative diabetic retinopathy, nephrotic syndrome, and cardiovascular/metabolic disorders. Due to its multifunctional activities and disease associations, ANGPTL4 is considered a promising therapeutic target and diagnostic/prognostic biomarker, but safety concerns remain, especially with respect to its effects on lipid metabolism, promotion of angiogenesis, and dual roles in malignancy.

Other names

Fasting-induced adipose factor (FIAF)Hypoxia-inducible factor (HFARP)Peroxisome proliferator-activated receptor gamma angiopoietin-related protein (PGAR)ANGPTL2 (former name)

Inhibition of lipoprotein lipase (LPL) to regulate plasma triglycerides and lipid uptake. Modulation of endothelial barrier function and vascular permeability. Promotion or inhibition of angiogenesis depending on context. Modulation of glucose metabolism and insulin sensitivity.