{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CNTNAP3 (also known as Caspr3) encodes a neural cell adhesion molecule that plays multifaceted roles in both the central nervous system and peripheral tissues. In the nervous system, genetic mutations or deletion of CNTNAP3 lead to altered synapse development by differentially regulating the formation of excitatory and inhibitory synapses. Loss‐of‐function mutations in CNTNAP3 have been linked to deficits in social interaction, impaired spatial learning, and the emergence of repetitive behaviors in mice, providing mechanistic insights into autism spectrum disorder pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, analysis of CNTNAP3‐null mice has revealed its involvement in motor learning, as these mutants exhibit delayed acquisition of motor skills accompanied by reduced neuronal activation in the dorsal striatum"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "; initial characterization also noted its specific expression along axons and interaction with PDZ‐domain proteins in areas such as the corpus callosum and other white matter tracts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in neurodevelopment, aberrations involving the CNTNAP3 gene have been observed in diverse pathological conditions. A circular RNA originating from the CNTNAP3 transcript (cCNTNAP3) acts as a tumor suppressor in esophageal squamous cell carcinoma by sponging miR‐513a-5p, thereby upregulating p53 and inhibiting proliferation and promoting apoptosis in p53 wild‐type cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Genomic deletions that encompass the CNTNAP3 gene have also been identified in testicular germ cell tumors, implicating it in tumor predisposition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In another context, CNTNAP3 has been shown to upregulate the autophagy gene ATG16L1 and increase autophagic vacuole formation, a finding that suggests it may contribute to cellular homeostasis in Crohn’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additionally, elevated expression levels of CNTNAP3 mRNA in peripheral leukocytes of schizophrenia patients point toward its involvement in neural network formation and autophagy regulation in psychiatric conditions"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and genetic linkage analyses have nominated CNTNAP3 as a candidate susceptibility gene for bipolar disorder."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, interactions between neuregulin 3 (NRG3) and CNTNAP3 have been implicated in the development of dopaminergic synapses, particularly within striatal medium spiny neurons, thereby influencing dopamine release and associated behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CNTNAP3 functions as a pivotal regulator of synapse formation, neural network integrity, and cellular homeostasis. Its dysregulation is associated with neurodevelopmental disorders such as autism, mood disorders including bipolar disorder, as well as various pathological conditions ranging from cancer to inflammatory diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Da-Li Tong, Rui-Guo Chen, Yu-Lan Lu, et al. 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