TLCD1 is a transmembrane lysophosphatidylethanolamine acyltransferase that regulates cellular phospholipid composition and membrane properties 1. The protein functions as a lipid acyltransferase with conserved catalytic histidine residues, structurally resembling ceramide synthases and fatty acid elongases 2. TLCD1 inhibits the incorporation of omega-3 long-chain polyunsaturated fatty acid (LCPUFA)-containing phospholipids into membranes, thereby promoting membrane rigidity without affecting LCPUFA synthesis itself 3. This regulatory mechanism compensates for dietary fatty acid variations and prevents lipotoxicity by controlling membrane fluidity 3. Clinically, TLCD1 demonstrates significant disease relevance across multiple contexts. High TLCD1 expression is associated with worse prognosis in glioblastoma and melanoma patients receiving anti-PD1 immunotherapy, positioning it as a potential immunotherapy response biomarker 4. TLCD1 expression correlates with cancer staging and prognosis in various malignancies and immune cell infiltration patterns 4. In hepatocellular carcinoma, TLCD1 inhibition by arsenic sulfide suppresses cell proliferation and migration while promoting apoptosis 5. These findings indicate TLCD1's dual importance in normal membrane homeostasis and cancer biology, making it a potential therapeutic target and prognostic biomarker.