DGAT1 catalyzes the terminal committed step in triglyceride synthesis, converting diacylglycerol and fatty acyl-CoA substrates into triglycerides. The enzyme is highly expressed in intestinal epithelium, where it is essential for dietary fat absorption, and in liver, where it facilitates fatty acid esterification and fat storage. DGAT1 also functions as a retinoid acyltransferase in skin, maintaining retinoid homeostasis and preventing toxicity. Beyond triglyceride synthesis, DGAT1 exhibits additional acyltransferase activities, including monoacylglycerol and wax ester synthesis. DGAT1 has emerged as a significant player in disease pathogenesis. In glioblastoma, DGAT1 upregulation protects tumor cells from lipotoxicity by sequestering excess fatty acids into triglycerides and lipid droplets; DGAT1 inhibition disrupts this homeostasis, triggering mitochondrial oxidative stress and apoptosis 1. Similar lipid-dependent survival mechanisms occur in clear cell renal cell carcinoma, where the JMJD6-DGAT1 axis drives lipid droplet formation and tumorigenesis 2, and in hepatocellular carcinoma, where DGAT1-dependent lipid accumulation in macrophages promotes immunosuppression and tumor growth 3. In acute myeloid leukemia, CDCA suppresses progression by activating the ROS/p38 MAPK/DGAT1 pathway, promoting lipid peroxidation 4. Clinical interest has focused on DGAT1 inhibitors, which show potential for metabolic diseases and cancers, though gastrointestinal effects have been observed 5. Pathogenic DGAT1 variants cause diarrhea and protein-losing enteropathy, establishing its clinical relevance in intestinal lipid metabolism.