The ZEB1–neuroinflammation axis plays a pivotal role in the pathogenesis of different CNS disorders, such as brain tumors, multiple sclerosis, cerebrovascular diseases, and neuropathic pain, by promoting tumor cell proliferation and invasiveness, formation of the hostile inflammatory micromilieu surrounding neuronal tissues, dysfunction of microglia and astrocytes, impairment of angiogenesis, and dysfunction of the blood–brain barrier. This evidence concerns the gene ZEB1 and multiple sclerosis.