Phosphatidic acid phosphatase (PAP)

Phosphatidic acid phosphatase (PAP) is a vital regulator of lipid homeostasis that catalyzes the Mg2+-dependent dephosphorylation of phosphatidic acid (PA) to produce diacylglycerol (DAG) [1, 4]. This enzymatic step is essential for the synthesis of triacylglycerol (TAG) and membrane phospholipids like phosphatidylcholine and phosphatidylethanolamine [5, 13]. In mammals, PAP activity is primarily mediated by the lipin family (Lipin-1, -2, and -3), which also act as transcriptional coactivators to regulate fatty acid oxidation [11, 16]. Mutations or dysregulation of these enzymes are associated with various human diseases, including obesity, lipodystrophy, and Majeed syndrome [1, 11]. Specifically, Lipin-1 deficiency is a known cause of acute recurrent rhabdomyolysis in children, while its overexpression promotes adiposity [11, 13]. Due to its central role in fat storage, PAP is considered a potential therapeutic target for obesity and metabolic disorders [4, 7]. Although no specific drugs are currently approved, compounds such as propranolol and sertraline are recognized as inhibitors used in research to study PAP function [7, 13].

Other names

Phosphatidate phosphatase3-sn-phosphatidate phosphohydrolaseLipinPAP-1PAP-2Lipid phosphate phosphataseLPP

Inhibition of the enzymatic conversion of phosphatidic acid to diacylglycerol to reduce triacylglycerol synthesis and modulate lipid signaling pathways [4, 7].