Adipose triglyceride lipase (ATGL)

Adipose triglyceride lipase (ATGL), encoded by the PNPLA2 gene, is a key enzyme responsible for the first and rate-limiting step of intracellular lipolysis—the hydrolysis of stored triglycerides into diacylglycerols and free fatty acids in lipid droplets. ATGL is highly specific for triglyceride substrates and plays a central role in energy homeostasis by mobilizing stored fats, especially during fasting or increased metabolic demand. The enzyme is tightly regulated by hormonal and protein-protein interactions, including activation by the co-activator ABHD5 (CGI-58) and inhibition by proteins such as G0S2. Defects or loss-of-function mutations in ATGL/PNPLA2 result in neutral lipid storage disorders with myopathy, while dysregulation is associated with broader metabolic diseases including insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, and inflammation. Experimental inhibitors such as Atglistatin are under development, but no clinically approved drugs target ATGL directly as of now[1][2][3][4].

Other names

Patatin-like phospholipase domain-containing protein 2PNPLA2DesnutrinTriglyceride hydrolaseCalcium-independent phospholipase A2-zetaTransport-secretion protein 2.2PEDF-R (Pigment epithelium-derived factor receptor)TTS2.2FP17548PLPL2_HUMAN

Inhibition of ATGL blocks the hydrolysis of triglyceride, reducing fatty acid release and downstream effects. Activation of ATGL increases lipolysis and fatty acid mobilization.