KCNH3 encodes Kv12.2, the pore-forming subunit of a voltage-gated inwardly rectifying potassium channel characterized by fast activation during depolarization followed by rapid inactivation through a C-type mechanism and rapid recovery from inactivation. The channel is primarily expressed in the nervous system, where it regulates neuronal excitability and membrane potential. Recent evidence demonstrates that KCNH3 loss-of-function variants cause neurodevelopmental disease. A de novo missense variant (p.Ala371Val) identified in an eight-year-old girl with global developmental delay, intellectual disability, autistic behavior, hyperactivity, insomnia, and nocturnal seizures showed loss-of-function with dominant-negative effects on wild-type channel subunits 1. Electrophysiological analysis revealed the mutant channels exhibited accelerated inactivation kinetics and a negative shift in inactivation voltage dependence, rendering loss of function voltage-dependent 2. KCNH3 variants have been identified in patients with microcephaly and neurodevelopmental disorders 34. Beyond neurodevelopmental disease, KCNH3 has been implicated in other pathologies: variants appear in aggressive prostate cancer genomes 5, and differential expression patterns have been observed in proliferative diabetic retinopathy 6. KCNH3 inhibition via ASP2905, a selective potassium channel antagonist, enhanced cognitive performance in rodent models, suggesting potential therapeutic applications in cognitive disorders 7.