These results are consistent with the concept that the induction of Puma is necessary for ER stress-induced apoptosis and can be linked to direct Bax activation, initiating mitochondrial dysfunction as a downstream consequence of ER stress.32 These results are in accordance with the high hepatic expression levels of Puma and Bax found in patients with NASH contributing to hepatocyte lipoapoptosis.33 Interestingly under stress conditions, Bax and Bak can activate IRE1α. Here, BAX is linked to metabolic dysfunction-associated steatohepatitis.