Phosphatidate cytidylyltransferase 2

Phosphatidate cytidylyltransferase 2 (CDS2) catalyzes the conversion of phosphatidic acid to CDP-diacylglycerol, a critical intermediate in the synthesis of phosphatidylglycerol, cardiolipin, and phosphatidylinositol (UniProt: O95674). The enzyme exhibits substrate specificity for particular acyl chain compositions and plays an important role in regulating lipid droplet growth and maturation, which are central to lipid and energy homeostasis.

CDS2 is involved in membrane lipid biosynthesis pathways essential for cellular function across tissues. The enzyme's role in lipid homeostasis connects it to broader metabolic processes that support cell viability and organellar dynamics.

CDS2 is significantly upregulated in Alzheimer's Disease brain tissue. In a human post-mortem AD brain proteomics study comparing affected tissue to age-matched controls using TMT-labeled quantitative mass spectrometry across multiple subcellular fractions, CDS2 showed a mean log2 fold-change of +1.319 (Chaparral AD proteomics). This upregulation suggests dysregulation of phospholipid metabolism in AD pathology, potentially reflecting compensatory lipid remodeling or abnormal accumulation of lipid intermediates in diseased brain.