{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNRN1, also known as neuritin or CPG15, is an activity‐regulated neurotrophic factor that plays a pivotal role in neural development and synaptic plasticity. It promotes neurite outgrowth, axonal extension, branching, and synapse formation, thereby supporting neuronal survival and the proper assembly of neural circuits. In motor neurons, NRN1 facilitates the local translation of key cytoskeletal mRNAs and promotes motor axon branching and neuromuscular junction formation, while in other neuronal populations it enhances dendritic spine density and supports synaptic resilience. In addition, NRN1 modulates intracellular signaling pathways—including Ca²⁺/calcineurin–NFAT and Notch—that are essential for ion channel regulation and adaptive responses following neural injury and degeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in development, NRN1 is increasingly recognized as a modulator of cognitive function and neural network stability in neuropsychiatric and neurodegenerative disorders. Genetic variation in NRN1 has been linked to alterations in fluid intelligence and working memory, and its expression patterns correlate with synaptic defects, neural hyperexcitability, and impaired cognitive resilience observed in conditions such as schizophrenia and Alzheimer’s disease. Moreover, epistatic interactions between NRN1 and other neuroplasticity‐related genes (for example, BDNF and dysbindin) highlight its contribution to the modulation of psychopathological profiles and regional brain structure."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence indicates that the function of NRN1 extends well beyond the nervous system. Its expression is induced under hypoxic conditions in vascular endothelial cells, and alterations in NRN1 promoter methylation have been linked to tumor progression in several malignancies—including astrocytoma, esophageal and gastric cancers, and malignant melanoma—where NRN1 influences cell migration, proliferation, angiogenesis, and resistance to apoptosis. In addition, experimental modulation of NRN1 in non‐neuronal cell types such as bone marrow–derived mesenchymal stem cells and endometriotic tissues suggests roles in cellular senescence, viability, and tissue remodeling. Preliminary findings also hint at potential involvement of NRN1 in the cellular responses to environmental stressors, such as noise-induced hearing loss."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tadahiro Fujino, Zhen Wu, Walter C Lin, et al. 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