We previously reported the importance of TAK1-mediated MAPK signaling pathway in regulating NASH.44 In this study, we confirmed that JNK/MAPK was required for tamoxifen to treat fatty liver disease, as tamoxifen inactivated JNK/MAPK signaling and JNK activator abolished the therapeutic effect of tamoxifen. The gene discussed is MAPK8; the disease is metabolic dysfunction-associated steatohepatitis.