USP25 is a DUB that is encoded by a gene located at 21q11.2.[21] Functionally, USP25 has been shown to participate in multiple inflammatory diseases including multiple sclerosis,[11] sepsis,[12] viral infection,[13] colitis,[15] pancreatitis,[14, 22] and Alzheimer's disease (AD).[16] In addition to inflammatory diseases, USP25 has emerged as a key regulator in cancer.[15, 23] In the present study, we found that USP25 ameliorated cerebral ischemic stroke injury, expanding the disease spectrum regulated by USP25. The gene discussed is ZUP1; the disease is multiple sclerosis.