Collectively, our findings in the CHIP−/−-livers reveal that in spite of the remarkably sustained CYP2E1-ROS-JNK1-c-Jun/AP-1-activation and the associated NAFLD/NASH-pathognomonic manifestations comparable to those seen in HF- and MCD-induced NAFLD/NASH murine models30, 31, 32, 33, 34, these livers remain largely resistant to NASH at the least over the initial 8–9 months of life. Here, JUN is linked to metabolic dysfunction-associated steatohepatitis.