CNTF, ciliary neurotrophic factor, was initially identified as a survival factor for cultured embryonic chick parasympathetic neurons. The rat protein has 84% similarity to the human and rabbit proteins. It lacks an N-terminal signal sequence and consensus sequences for glycosylation or hydrophobic regions. The CNTF profile shows similar sequence and structure motifs to hematopoietic cytokines (IL-6, IL-11, LIF, oncostatin M, cardiotrophin-1) and thus was considered a member of the IL-6 family. CNTF exerts effects on glial cells and neurons; CNTF activates astrocytes, which promote their capacity to support neurons and oligodendroglia. CNTF stimulates astrocytes to secrete FGF-2 and rat microglia to secrete glial cell line-derived neurotrophic factor (GDNF). CNTF is produced by astrocytes after brain injury. The CNTF receptor complex includes the CNTF binding protein (CNTFRα), and two signaling chains leukemia inhibitory factor receptor β (LIFRβ) and the signal transducer of IL-6 (gp130). CNTFRα does not have transmembrane or intracellular domains, which means it does not induce signal transduction per se. CNTFRα is associated to the cell membrane via glycosyl phosphatidylinositol linkage, and it can be released by phospholipase C to produce a soluble receptor. The complex formed by CNTFRα and CNTF serve as agonists for cells that do not express CNTFRα. In addition, human CNTF can recruit and activate another receptor in this case CNTFRα is substituted by IL-6Rα. Cardiotrophin-like cytokine (CLC) also binds to CNTFRα, which activates the gp130 and LIFRb subunits. CNTF reduces the symptoms of experimental autoimmune encephalomyelitis, and its absence exacerbates the severity of multiple sclerosis disability. CNTF has been studied in retinal degenerative disorders and was shown to have a potential clinical application.