Uncoupling protein plays a vital role in ETC uncoupling to regulate ATP synthesis, the NAD+/NADH ratio, and other metabolic pathways.89 Uncoupling protein-2 (UCP2) is a mitochondrial inner membrane protein related to oxidative stress.90 Under physiologic conditions, UCP2 is expressed in Kupffer cells rather than hepatocytes.91 However, it becomes abundant in hepatocytes of fatty liver.92 Suppression of UCP2 limits hepatic IRI in ob/ob mice.93 These findings indicate that UCP2-dependent mitochondria uncoupling seems an essential factor in NASH development. The gene discussed is UCP2; the disease is metabolic dysfunction-associated steatohepatitis.