{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Ciliary neurotrophic factor receptor (CNTFR) is emerging as a key component within several multiprotein receptor complexes that mediate a wide range of cytokine‐dependent functions in both neural and non‐neural tissues. In neural cells, CNTFR forms a receptor complex together with gp130 and LIFR to mediate the actions of ciliary neurotrophic factor (CNTF), Humanin, and cardiotrophin‐like cytokine factors – signals that are critical for neuronal survival, neuroprotection, and neuroplasticity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " \n Beyond its neurotrophic roles, CNTFR‐mediated signaling has been implicated in diverse physiological processes. In skeletal muscle and bone, genetic variations in CNTFR are associated with differences in fat‐free mass and strength, and CNTFR signaling in osteoblasts influences bone growth and morphology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " \n Moreover, CNTFR signaling appears to contribute to oncogenesis; for example, activation of the CLCF1–CNTFR axis has been shown to drive tumor cell behavior in lung adenocarcinoma, while its blockade can inhibit tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " \n In the neuroendocrine arena, genetic studies have linked variants in CNTFR not only to susceptibility for eating disorders but also to altered age‐at‐onset and body composition traits, suggesting a role in integrating metabolic and behavioral responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " \n Structural analyses further reveal that CNTFR interacts with gp130 and LIFR to form a device that, although not itself signaling, is indispensable for high‐affinity ligand binding and subsequent activation of downstream signaling pathways – insights that have guided the engineering of CNTF variants with receptor selectivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " \n Finally, mutations in ligands that signal via CNTFR, such as in the case of Crisponi syndrome arising from defects in CLCF1/CRLF1, underscore the developmental importance of this receptor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings establish CNTFR as a multifunctional mediator that integrates neurotrophic, metabolic, and oncogenic cues, thereby influencing neuronal survival, muscle and bone physiology, as well as tumorigenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuichi Hashimoto, Megumi Kurita, Sadakazu Aiso, et al. 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