Phosphatidate cytidylyltransferase 1 (CDS1)

Phosphatidate cytidylyltransferase 1 (CDS1) is an **integral membrane enzyme** encoded by the CDS1 gene in humans, primarily responsible for catalyzing the conversion of phosphatidic acid (PA) and cytidine triphosphate (CTP) to CDP-diacylglycerol (CDP-DAG), a critical precursor in the biosynthesis of major phospholipids, including phosphatidylinositol (PI) and cardiolipin (CL)[1][2][3]. CDS1 is localized to the inner mitochondrial membrane and the endoplasmic reticulum, supporting both mitochondrial and cytoplasmic phospholipid synthesis. By regulating the supply of CDP-DAG, CDS1 plays a **rate-limiting role** in the formation of phosphoinositides (key signaling molecules downstream of many receptors) and mitochondrial cardiolipin (essential for mitochondrial structure and function)[1][2]. Loss or downregulation of CDS1 leads to impaired lipid signaling and synthesis, alterations in lipid droplet size (resulting in supersized lipid droplets), defects in cellular proliferation or differentiation, and can drive metabolic and tumorigenic changes[2][3]. While no direct small-molecule drugs for CDS1 are established, it is emerging as an important locus for metabolic regulation and potentially as a target in diseases characterized by dysregulated lipid metabolism or signaling[2][3].

Other names

CDP-diacylglycerol synthase 1CDP-DAG synthase 1CDP-diglyceride pyrophosphorylase 1CDP-diglyceride synthase 1CTP:phosphatidate cytidylyltransferase 1cytidine diphosphate diacylglycerol synthase 1phosphatidate cytidylyltransferase 1CDS (for short)

Inhibition or genetic disruption leads to decreased phosphatidylinositol and cardiolipin synthesis, altered cell signaling, lipid metabolism derangements, and impaired cell growth[2][3].