PCYT1B catalyzes the rate-limiting step of the CDP-choline (Kennedy) pathway for phosphatidylcholine (PC) biosynthesis 1. Located on the endoplasmic reticulum, this choline-phosphate cytidylyltransferase converts choline phosphate to CDP-choline, a critical intermediate in PC synthesis 1. Mechanistically, PCYT1B functions downstream of p53 in regulating lipid droplet (LD) homeostasis. During choline depletion, p53 upregulates PCYT1B to direct available choline toward PC biosynthesis, preventing LD coalescence and excessive fatty acid mobilization 1. Loss of p53 impairs this response, leading to dysregulated choline metabolism, LD expansion, and hepatic steatosis 1. Clinically, PCYT1B variants have been investigated in neonatal respiratory distress syndrome (RDS), where PC deficiency in pulmonary surfactant contributes to pathology. However, studies in Chinese Han populations found no significant association between PCYT1B mutations and RDS susceptibility 23. A rare Xp22.11 deletion affecting PCYT1B was associated with craniosynostosis and periventricular nodular heterotopia in one male patient 4. PCYT1B has also been identified as a candidate gene in galactose-induced cataract formation, though expression changes remain unclear 5. These findings underscore PCYT1B's essential role in PC-dependent lipid metabolism and tumor suppression pathways.