DGAT1 (diacylglycerol O-acyltransferase 1) catalyzes the terminal committed step of triacylglycerol synthesis, converting diacylglycerol and fatty acyl-CoA into triglycerides 12. The enzyme is highly expressed in small intestinal epithelium, where it is essential for dietary fat absorption, and in liver, where it facilitates fatty acid esterification and storage 21. DGAT1 also functions as a major acyl-CoA retinol acyltransferase in skin, maintaining retinoid homeostasis 1. Beyond triglyceride synthesis, DGAT1 exhibits broader acyltransferase activities including monoacylglycerol and wax ester synthesis 3. Recent research reveals DGAT1's critical role in disease pathogenesis. In cancer models, DGAT1 upregulation protects glioblastoma and renal cell carcinoma cells by sequestering excess fatty acids into lipid droplets, preventing lipotoxicity and oxidative stress 45. In leukemia, DGAT1 upregulation promotes lipid droplet accumulation and lipid peroxidation via ROS/p38 MAPK signaling 6. In hepatocellular carcinoma, DGAT1-mediated lipid droplet formation in tumor-infiltrating macrophages supports their survival and promotes immunosuppressive Treg recruitment 7. Notably, DGAT1 is nonessential for survival, contrasting with DGAT2 8. Disease associations include protein-losing enteropathy and diarrhea, reflecting its intestinal function 9. The emerging therapeutic potential of DGAT1 inhibition across metabolic and oncologic contexts reflects its central role in lipid homeostasis and immune regulation.