{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KCNC2, which encodes the Kv3.2 voltage‐gated potassium channel subunit, plays a critical role in rapid membrane repolarization that enables high‐frequency neuronal firing and precise action potential repolarization. During early postnatal development, Kv3.2 is expressed in defined populations of fast‐spiking GABAergic interneurons to help shape the brief action potentials that are essential for synchronized network activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In thalamocortical neurons, for example, the activity of Kv3.2 channels is fundamental to achieving maximal firing rates by efficiently repolarizing the membrane following depolarization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Aberrant regulation of KCNC2 has been implicated in several neurological disorders. In hippocampal CA3 pyramidal neurons derived from bipolar disorder patients, overexpression of KCNC2 (together with KCNC1) correlates with a hyperexcitable phenotype in lithium‐responsive individuals; pharmacological blockade of fast potassium currents attenuates this hyperexcitability, while long‐term lithium treatment normalizes the firing behavior by reducing these currents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, deletions in genomic regions encompassing KCNC2—as well as de novo missense mutations in the gene—have been associated with neurodevelopmental delay, cerebellar ataxia, and developmental epileptic encephalopathies, underscoring its essential role in normal neuronal function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in excitability and signal timing, recent multi‐omics studies have revealed that KCNC2 may also contribute to metabolic regulation. Reduced expression of KCNC2 is linked to heightened endoplasmic reticulum stress and increased hepatic gluconeogenesis in obesity‐induced insulin resistance, suggesting that normal Kv3.2 function exerts anti‐obesogenic effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, modulation of Kv3.2 activity has been shown to influence neuronal network oscillations. Small‐molecule compounds that target Kv3.1/Kv3.2 channels can rescue disrupted gamma oscillations—critical for cognitive processes—in disease models, highlighting the channel’s importance in synchronizing fast neuronal networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, neurotrophin signaling via TrkB receptors has been found to affect Kv3.2 expression and phosphorylation in cortical interneurons, linking extrinsic growth factor cues to intrinsic excitability regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings demonstrate that KCNC2 is a key molecular determinant of rapid repolarization and high‐frequency firing in neurons. Its proper function is indispensable not only for maintaining the temporal fidelity of neuronal signaling but also for supporting network synchrony and potentially modulating metabolic homeostasis. Disruptions in KCNC2 expression or function contribute to a spectrum of neurological and metabolic disorders, making it a compelling target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Emily Phillips Tansey, Alan Chow, Bernardo Rudy, et al. 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