Phosphatidate cytidylyltransferase 2 (CDS2)

Phosphatidate cytidylyltransferase 2 (CDS2) is an integral membrane enzyme that catalyzes the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid and CTP, a crucial step in the biosynthesis of phosphatidylinositol, phosphatidylglycerol, and cardiolipin[1][2][3][5]. CDS2 localizes mainly to the endoplasmic reticulum and is broadly expressed, playing a central role in the regulation of phosphoinositide pools used in cell signaling downstream of G protein-coupled receptors and tyrosine kinases[1][3]. The enzyme exhibits substrate selectivity for specific acyl chains in phosphatidic acid, with a preference for 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid[5]. Loss or reduction of CDS2 disrupts phosphoinositide balance, altering cell morphology, cytoskeletal organization, and mitochondrial structure[2]. Mutations have been associated with rare forms of congenital muscular dystrophy, intellectual disability, and cortical malformations[3]. No drugs targeting CDS2 are known, but its central metabolic role suggests it could be a therapeutic target in diseases involving lipid signaling and mitochondrial dysfunction.

Other names

Phosphatidate cytidylyltransferase 2CDP-diacylglycerol synthase 2CDP-DAG synthase 2CDP-DG synthase 2CDP-diglyceride pyrophosphorylase 2CTP:phosphatidate cytidylyltransferase 2cytidine diphosphate diacylglycerol synthase 2CDS 2

Not applicable (no direct inhibitors or activators known in the clinic as of now)