Angiopoietin-related protein 4 (ANGPTL4) (ANGPTL4)

Angiopoietin-related protein 4 (ANGPTL4) is a secreted glycoprotein that plays a central role in the regulation of lipid and glucose metabolism [1, 16]. It is primarily expressed in adipose tissue and the liver and functions as a potent inhibitor of lipoprotein lipase (LPL), the enzyme responsible for clearing triglyceride-rich lipoproteins from the blood [1, 6]. By inhibiting LPL, ANGPTL4 increases circulating triglyceride levels, and genetic loss-of-function variants in humans are linked to lower triglycerides and a reduced risk of coronary artery disease and type 2 diabetes [11, 15]. Beyond its metabolic functions, ANGPTL4 is involved in modulating angiogenesis, vascular permeability, and inflammation, often in a context-dependent manner [2, 3, 8]. In oncology, it is frequently upregulated in various cancers and can promote tumor progression and metastasis, while in ophthalmology, it contributes to pathological neovascularization in conditions like diabetic retinopathy [16, 18, 19]. Therapeutic strategies targeting ANGPTL4 include monoclonal antibodies and antisense oligonucleotides aimed at treating severe hypertriglyceridemia and reducing cardiovascular risk [11, 14, 15]. While early animal studies raised safety concerns regarding mesenteric lymphadenopathy, recent clinical trials have shown promising safety and efficacy profiles in humans [11, 12, 17].

Other names

Angiopoietin-like protein 4Fasting-induced adipose factor (FIAF)Hepatic fibrinogen/angiopoietin-related protein (HFARP)PPARG angiopoietin-related protein (PGAR)

Inhibition of ANGPTL4 to increase lipoprotein lipase (LPL) activity, thereby lowering plasma triglycerides and remnant cholesterol; inhibition of ANGPTL4 to suppress pathological angiogenesis and vascular leakage.