{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNEXMIF, formerly known as KIAA2022, is an X‐linked gene that is highly expressed in the developing brain and has emerged as a critical regulator of neurodevelopment. Multiple studies have demonstrated that reduction in NEXMIF function is associated with impaired neuronal formation; for example, targeted knockdown in cultured rat hippocampal neurons disrupted neurite outgrowth—affecting both dendritic and axonal processes—and provided early evidence linking NEXMIF to proper brain wiring and intellectual development. These findings are consistent with early observations in cases of mental retardation, where genetic causes remain to be elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the cellular level, experimental models have further characterized the role of NEXMIF in regulating neurite extension and migration. In studies using PC12 cells, NEXMIF (also referred to as Xpn) was found to modulate cell–cell and cell–matrix adhesion by controlling the expression of adhesion molecules such as N‐cadherin and β1‐integrin. The resulting dysregulation of cell adhesion disrupts cellular migration, a process essential for correct neuronal network formation. Complementary genetic screens in patients have reinforced the link between loss‐of‐function mutations and deficits in neurite outgrowth, thereby establishing NEXMIF as vital for normal neural connectivity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, a spectrum of neurodevelopmental disorders—including intellectual disability, autism spectrum behaviors, epilepsy, and developmental delay—has been observed in patients with truncating or deleterious mutations in NEXMIF. These observations span both males and females, with affected males generally displaying more severe phenotypes, and are supported by several clinical case series and reviews. Such studies extend the functional significance of NEXMIF beyond neurite outgrowth, implicating its loss in disrupted neuronal migration and defective cell adhesion during development. Ongoing research continues to delineate the expanded phenotypic spectrum, including subtle dysmorphic and additional neurological features, underscoring the gene’s critical contribution to brain development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "V Cantagrel, A-M Lossi, S Boulanger, et al. 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