CNTF is a member of the four-helix bundle cytokine family and is structurally related to other family members such as IL-6, IL-11, and LIF. Binding of CNTF to its receptor CNTFRα triggers the association with the IL-6 receptor gp130 and the LIF receptor LIFRβ, followed by activating the JAK-STAT, the ERK, and the PI3K signaling pathways. CNTF was first identified as a neuroprotective factor that supported the survival of embryonic chick ciliary neurons. CNTF has been shown to regulate the differentiation and survival of a variety of neuronal cells and has been applied as the treatment for retinal degenerative diseases caused by genetic defect or damage induced by toxins, auto-antibodies, or strong light. CNTF is also revealed as a myotrophic factor for denervated skeletal muscle and a modulator for AMPK-mediated energy balance control.