KCNH1 encodes Kv10.1, a voltage-gated delayed rectifier potassium channel predominantly expressed in the central nervous system that mediates outward-rectifying potassium currents without inactivation. The channel's activation kinetics are voltage-dependent and modulated by divalent cation concentration and subunit assembly, with biphasic activation kinetics comprising fast and slow components. Beyond ion transport, KCNH1 regulates cell proliferation and differentiation, particularly adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells. Pathogenic gain-of-function variants in KCNH1 cause a spectrum of neurodevelopmental disorders ranging from isolated epilepsy to syndromic encephalopathy 1. De novo mutations decrease the activation threshold and delay deactivation of the channel 2, and variants clustering in transmembrane domains S4 and S6 are associated with epileptic encephalopathy, while scattered variants elsewhere correlate with milder isolated seizures or syndromes without epilepsy 3. KCNH1 variants cause Temple-Baraitser syndrome and Zimmermann-Laband syndrome characterized by developmental delay, intellectual disability, facial dysmorphism, infantile-onset seizures, and gingival fibromatosis 4. Recent evidence suggests KCNH1 localizes to primary ciliary structures and that pathogenic variants perturb ciliogenesis and sonic hedgehog signaling 5. Oncogenically, KCNH1 expression is upregulated in cervical and renal cancers downstream of HPV oncogenes and SLC17A9, respectively, promoting tumor growth and correlating with poor prognosis 6, 7. Therapeutic approaches under development include allosteric modulators inducing depolarizing shifts in activation threshold for seizure control in KCNH1 epilepsy 1, with emerging interest in targeting KCNH1 expression as an adjuvant cancer strategy.