{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCNT1 encodes a sodium‐activated potassium channel (also known as Slack) that plays a critical role in regulating neuronal excitability by modulating potassium currents during repolarization. Gain‐of‐function mutations in KCNT1 consistently lead to an abnormal increase in channel activity—either by constitutive activation or by altered sodium sensitivity and enhanced cooperative channel gating—which perturbs the normal regulation of action potentials. Such dysregulation has been implicated in a broad spectrum of severe early‐onset epileptic encephalopathies, including malignant migrating partial seizures of infancy, autosomal dominant nocturnal frontal lobe epilepsy, and epilepsy of infancy with migrating focal seizures."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to directly modulating ion flux, the C‐terminal domain of KCNT1 mediates non‐conducting interactions with cytoplasmic proteins that participate in developmental signaling. This dual role may contribute further to neurodevelopmental abnormalities seen in patients harboring KCNT1 mutations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, pharmacological agents such as quinidine have shown promise in reducing the excessive channel activity associated with these mutations, highlighting the potential for targeted therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Notably, individual KCNT1 mutations can exhibit considerable phenotypic heterogeneity even within the same family, suggesting a complex genotype–phenotype relationship that contributes to differences in clinical presentation and severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Overall, KCNT1 is essential for maintaining the proper balance of neuronal excitability during development and adult function, and its perturbation underlies several devastating epileptic syndromes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Giulia Barcia, Matthew R Fleming, Aline Deligniere, et al. 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