CNTFR (ciliary neurotrophic factor receptor) is a glycosyl-phosphatidylinositol-anchored receptor protein located on chromosome 9 that mediates neuroprotective signaling. It functions as the alpha subunit providing receptor specificity within a tripartite complex with gp130 and LIFR-beta 1. CNTFR binds ciliary neurotrophic factor (CNTF), a glial cell-derived cytokine that promotes survival and differentiation of sensory, sympathetic, motor, and ciliary neurons 1. The receptor also participates in humanin signaling as part of a complex with IL6ST and IL27RA 2. Ligand binding triggers JAK-mediated tyrosine phosphorylation of beta subunits, recruiting and activating STAT proteins that translocate to the nucleus to enhance gene transcription 1. CNTFR demonstrates selective expression in nervous system and skeletal muscle tissues. Loss of CNTFR causes perinatal lethality in mice, indicating developmental importance 1. In peripheral neuropathies, CNTFR-alpha mRNA levels correlate with demyelinating pathology and macrophage infiltration, suggesting roles in nerve regeneration 3. Beyond neurology, CNTFR variants associate with athletic sprint/power performance 4, and genetic analysis identifies CNTFR as a protective factor against dilated cardiomyopathy 5. CNTFR dysfunction contributes to Crisponi/cold-induced sweating syndrome when its ligands (CRLF1/CLCF1) are mutated 6.