CHPT1 (choline phosphotransferase 1) catalyzes the final step of de novo phosphatidylcholine (PC) synthesis by transferring choline phosphate from CDP-choline to diacylglycerol, playing a central role in formation and maintenance of vesicular membranes 1. This enzyme is essential for autophagosome membrane composition and turnover during autophagy-induced stress responses 2. Functionally, CHPT1 acts as a metabolic gatekeeper regulating cellular adaptation to adverse conditions. Disease relevance is substantial: mutations in CHPT1 cause globozoospermia, a severe form of male infertility characterized by abnormal sperm morphology 3. Additionally, CHPT1 dysregulation contributes to cancer chemoresistance and therapy evasion. In colorectal cancer, CHPT1 overexpression increases PC content and confers chemoresistance; elevated CHPT1 correlates with poor patient outcomes 4. Similarly, in prostate cancer, aberrantly activated enhancers upregulate CHPT1 expression, conferring resistance to antiandrogen therapy 5. In breast cancer, estrogen receptor-α directly regulates CHPT1 to reprogram choline metabolism and promote tumor growth and metastasis 6. CHPT1 dysregulation is also identified in sepsis pathogenesis 7. Clinically, CHPT1 represents a therapeutic target: inhibiting PC biosynthesis upstream of CHPT1 using edelfosine enhances chemosensitivity in resistant colorectal cancer models 4.