A potential additional benefit of inhibiting SREBP expression in the liver, independent of the reduction in hepatic TGs, is the reduced expression of PNPLA3. Polymorphisms in PNPLA3 are associated with hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma in humans (Romeo et al., 2008; Speliotes et al., 2010). Here, PNPLA3 is linked to metabolic dysfunction-associated steatohepatitis.