KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2, which functions as a pore-forming alpha subunit that mediates outward-rectifying potassium currents 1. The channel exhibits delayed rectifier properties with slow activation kinetics and voltage-dependent gating that begins at negative voltages, with activation rates dependent on holding potential and prepulse conditions 1. KCNH5 plays a critical role in neuronal excitability and brain function, as pathogenic variants in the voltage-sensing and pore domains cause developmental and epileptic encephalopathy 112 1. Clinical manifestations range from self-limited epilepsy with normal cognition to severe infantile-onset encephalopathy with profound disability, showing genotype-phenotype correlations 1. The channel demonstrates functional crosstalk with other KCNH subfamily members, where gain-of-function mutations can affect heteromeric channel complexes and alter neuronal membrane potential 2. Beyond neurological disorders, KCNH5 has been implicated as an autism spectrum disorder susceptibility gene 3 and shows tissue-specific expression patterns, including placenta-specific retrotransposon-derived transcripts that are aberrantly expressed in melanoma through hypomethylation 4. The channel also serves as a potential cardiac targeting mechanism and may contribute to pancreatic duct epithelial cell function 56.