PTDSS1 (phosphatidylserine synthase 1) catalyzes a base-exchange reaction replacing the polar head group of phosphatidylcholine (PC) or phosphatidylethanolamine (PE) with L-serine, primarily converting PC to phosphatidylserine (PS) 12. This enzyme localizes to the endoplasmic reticulum membrane and functions as a membrane-bound transferase. Mechanistically, PTDSS1 contains 10 transmembrane helices with a catalytic core in the luminal leaflet, operating similarly to membrane-bound O-acyltransferase family members 3. PS produced by PTDSS1 mediates immunosuppressive signaling, and loss of PTDSS1 increases interferon-γ-regulated genes and MHC-I expression, enhancing CD8+ T cell cytotoxicity 4. PTDSS1 also promotes aerobic glycolysis and malignant progression through PKM2-mediated nuclear-mitochondrial crosstalk 5. Clinically, gain-of-function PTDSS1 mutations cause Lenz-Majewski hyperostotic dwarfism, characterized by cutis laxa, skeletal dysplasia, and intellectual disability 6. In cancer, PTDSS1 is upregulated in esophageal squamous cell carcinoma, lung cancer, and bladder carcinoma with poor prognostic implications 78. PTDSS1 inhibition emerges as a therapeutic strategy, improving anti-PD-1 immunotherapy response and potentially lowering blood cholesterol through LDL receptor upregulation 43. Targeting PTDSS1 also reduces tumor-associated macrophage infiltration and tumor growth 9.