The TAK1 downstream IKKβ–IκBα–P65 axis is maintained in a continuously activated state during the pathogenesis of hepatic steatosis with high levels of systematic and local cytokine productions, which, combined with free fatty acids, can trigger the activation of JNK1/2 MAPK cascade, leading to the subsequent insulin dysfunction and abnormal fatty acid accumulation in the liver24, 51, 52. The gene discussed is IKBKB; the disease is fatty liver disease.