{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Fibroblast growth factor 22 (FGF22) is emerging as a multifunctional, target‐derived signaling molecule with critical roles in both the central nervous system and peripheral tissues. In the brain, FGF22 acts as a presynaptic organizer that specifically promotes the differentiation of excitatory nerve terminals. It is secreted by postsynaptic neurons in regions such as the hippocampus and cerebellum, thereby directing the clustering of synaptic vesicles and shaping synaptic circuitry; indeed, loss of FGF22 leads to decreased excitatory synapse formation and is associated with resistance to epileptic seizures."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, FGF22 is required for proper circuit remodeling after central nervous system injury, as its deficiency impairs new synapse formation and delays the molecular maturation of regenerating synapses"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and it induces the expression of insulin-like growth factor 2 (IGF2) in presynaptic neurons, thereby stabilizing these terminals in an activity‐dependent manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the skin, FGF22 is expressed by keratinocytes and hair follicle cells, with its mRNA being detectable during cutaneous development and upregulated at later stages of wound healing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Although FGF22 is dispensable for normal epidermal development and unchallenged skin repair, its presence appears to contribute to papilloma formation under carcinogenic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its classical roles in synaptogenesis and tissue repair, FGF22 has been implicated in the regulation of affective behavior. Studies indicate that FGF22 modulates the expression of pro-inflammatory cytokines such as interleukin-1β in the hippocampus, with enhanced FGF22 signaling correlating with reduced depression-like behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, aberrant FGF22 expression is linked to oncogenesis, as higher levels of FGF22 are associated with poor overall survival in lung adenocarcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and copy number duplications at the FGF22 locus have been identified as candidate risk factors in congenital heart diseases such as pulmonary atresia with ventricular septal defect."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the pleiotropic functions of FGF22 as it orchestrates excitatory synapse differentiation, facilitates synaptic and circuit remodeling post-injury, contributes to epithelial repair and tumorigenesis in the skin, and modulates mood-related behavior. The diverse roles of FGF22 highlight its potential as a therapeutic target in neurological disorders, wound repair, and cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hisashi Umemori, Michael W Linhoff, David M Ornitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FGF22 and its close relatives are presynaptic organizing molecules in the mammalian brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2004.06.025"}], "href": "https://doi.org/10.1016/j.cell.2004.06.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15260994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15260994"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Akiko Terauchi, Erin M Johnson-Venkatesh, Anna B Toth, et al. 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