ATF4 and hepatocellular carcinoma: Indeed, loss of ATF4 enhances liver damage.29 Unlike HFD-fed BL6 mice, which develop simple or benign steatosis, HFD-fed MUP-uPA mice progress to steatohepatitis, liver damage, and fibrosis owing to ER stress-driven hepatocyte death.7 The results described above suggest that ATF4 attenuates the progression from simple steatosis to NASH and HCC by suppressing ferroptosis, thereby blocking liver damage and necroinflammation.