MOGAT3 catalyzes the acylation of monoacylglycerol and diacylglycerol to synthesize diacylglycerol and triacylglycerol, respectively, with preference for palmitoyl-CoA and oleoyl-CoA substrates 1. The enzyme localizes to endoplasmic reticulum membranes and plays a key role in dietary fat absorption by facilitating triacylglycerol resynthesis in intestinal enterocytes 2. MOGAT3 expression is dynamically regulated in liver and is highly correlated with hepatic monoacylglycerol acyltransferase activity 1. Clinically, MOGAT3 dysregulation associates with multiple pathological conditions. In BRAFV600E-mutant metastatic colorectal cancer, MOGAT3-mediated diacylglycerol accumulation drives acquired resistance to anti-BRAF/anti-EGFR therapy by activating PKCα/CRAF/MEK/ERK signaling and increasing HIF1A expression; reducing intratumoral diacylglycerol with fenofibrate or PF-06471553 restored treatment efficacy 3. Similarly, in gastric intestinal metaplasia, MOGAT3 upregulation contributes to aberrant triglyceride and lipid droplet accumulation, with lipid synthesis inhibitors showing therapeutic potential 4. MOGAT3 overexpression also occurs in nonalcoholic fatty liver disease and correlates with obesity-related metabolic dysfunction 1. Selective MOGAT3 inhibitors represent a promising therapeutic strategy for metabolic and malignant diseases involving dysregulated lipid synthesis.