EIF2AK3 and obesity due to melanocortin 4 receptor deficiency: Increased activation of the ER stress response has been reported in obese mice and humans.3, 4, 7, 8 Obesity results in liver ER stress, which promotes insulin resistance and hepatosteatosis through the IRE1α branch.3 Moreover, PERK and IRE1α can regulate lipid stores in the liver, enforcing the hepatic metabolic disorders associated with obesity.9, 10 It is well established that apoptosis and inflammation are increased in patients with NASH, correlating with histological severity.