{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTXBP1 (Munc18‑1) is a highly conserved regulator of exocytosis that plays a central role in synaptic vesicle release. It functions by binding to syntaxin in its “closed” conformation, thereby acting as a molecular chaperone and regulator of SNARE‐complex assembly. Biophysical and structural studies have revealed that STXBP1 employs distinct binding mechanisms—including promoting step‐wise zippering of key SNARE proteins—to mediate vesicle docking and membrane fusion. In addition, experiments using fluorescence and single‐molecule force spectroscopy techniques have demonstrated that proper STXBP1–syntaxin interactions are essential for preserving protein stability and for the precise regulation of neurotransmitter release in neurons."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDiverse clinical and experimental studies have linked mutations in STXBP1 to a broad spectrum of neurodevelopmental and epileptic disorders. Multiple independent genetic investigations in patients have shown that heterozygous missense, truncating, or microdeletion events affecting STXBP1 give rise to early infantile epileptic encephalopathies—including Ohtahara and West syndromes—as well as nonsyndromic intellectual disability, sometimes accompanied by features reminiscent of schizophrenia or Rett‐like phenotypes. Animal models and patient‑derived neurons consistently demonstrate that STXBP1 haploinsufficiency leads to marked reductions in protein levels and consequent decreases in both spontaneous and evoked neurotransmitter release, underscoring its indispensability for proper neuronal network function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in neuronal exocytosis, emerging evidence implicates STXBP1 in the regulation of non‐neuronal secretory events and in modulating disease processes. Altered post‑translational modifications and decreased protein stability have been documented in contexts such as Alzheimer’s disease, where oxidative modifications of STXBP1 may contribute to the pathology. Furthermore, proteomic and genetic analyses have uncovered roles for STXBP1 in endocrine secretion and immune cell degranulation, highlighting its functional versatility and potential as a therapeutic target. Recent large‑scale phenotype mappings and mouse model studies are beginning to delineate the multifaceted impacts of STXBP1 dysregulation, paving the way for precision‐medicine approaches in several neurodevelopmental and neurodegenerative disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "K Gengyo-Ando, H Kitayama, M Mukaida, et al. 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