Results: In this study, we identified The RING finger 157 (RNF157) as a vital regulator of CD4+ T cell differentiation; it promoted Th1 differentiation but attenuated Th17 differentiation and CCR4 and CXCR3 expressions in CD4+ T cells, thereby limiting experimental autoimmune encephalomyelitis development. Here, RNF157 is linked to experimental autoimmune encephalomyelitis.