Phase II clinical trials confirm DGAT2 inhibition (ION224) significantly improves liver steatosis and histology in MASH patients. Animal models show DGAT2 inhibition increases ER phosphatidylethanolamine (PE) levels, suppressing SREBP-1c cleavage and lipogenesis. Cellular models indicate Seipin loss reduces cholesterol-mediated large LD formation and alleviates ER stress. This evidence concerns the gene SREBF1 and fatty liver disease.