ANGPTL4

Class

ANGPTL4 inhibitor (monoclonal antibody)

ANGPTL4 (angiopoietin-like 4) is a secreted protein that regulates lipid metabolism by inhibiting lipoprotein lipase (LPL), the enzyme that breaks down triglycerides carried in circulating lipoproteins so their fatty acids can be taken up by tissues. By suppressing LPL activity, ANGPTL4 shifts the balance toward retaining triglycerides in the bloodstream rather than clearing them, and its expression rises during fasting and varies with diet composition. Human genetic studies have identified loss-of-function variants in ANGPTL4 associated with lower circulating triglycerides and a reduced incidence of coronary artery disease, providing a genetic rationale for pharmacologically inhibiting this target to improve lipid profiles and cardiometabolic risk. Monoclonal antibodies directed against ANGPTL4 are designed to relieve its inhibitory effect on LPL, thereby promoting clearance of triglyceride-rich lipoproteins from plasma. This mechanism is of interest mainly for dyslipidemia and other disorders of triglyceride metabolism, and more broadly for conditions involving abnormal energy partitioning between tissues. Because ANGPTL4 also participates in fatty acid handling within the intestine and other organs, its inhibition raises distinct biological considerations compared with other lipid-lowering strategies, an important factor in the development of this mechanism.