Finally, our study has sound physiological and pathological relevance to autoimmune diseases, given the fact that a variety of human autoimmune diseases, including systemic lupus erythematosus, inflammatory bowel disease, and rheumatoid arthritis, are subjected to fine regulation by CRLs [55], whose activation requires neddylation E2, UBE2M/UBE2F, and E3 RBX1/RBX2. Here, UBE2M is linked to systemic lupus erythematosus.