KCNG4 encodes Kv6.4, a regulatory subunit of voltage-gated potassium channels that does not form functional channels independently but instead modulates heteromeric Kv2.1-containing channels. When coassembled with KCNB1 (Kv2.1), KCNG4 reduces the deactivation rate, shifts the activation threshold approximately 20 mV in the hyperpolarizing direction, and markedly shifts voltage-dependent inactivation approximately 40 mV hyperpolarized while accelerating activation kinetics 1. Recent evidence reveals KCNG4's role in nociception: the rare variant Kv6.4-Met419 exhibits dominant-negative effects, fails to traffic to the plasma membrane, and when overexpressed in uterine sensory neurons, increases action potential threshold and influences labor pain perception 2. KCNG4 variants have been associated with migraine susceptibility; the Kv6.4-L360P variant almost completely abolishes Kv2.1 currents, potentially initiating migraine pathology in the trigeminal system 3. Dorsal root ganglion neurons predominantly express Kv2/Kv6.4 heteromeric channels that are resistant to the Kv2-selective pore-blocker RY785 but sensitive to guangxitoxin-1E 4. Given KCNG4's role in regulating neuronal excitability, potassium channel modulators including amifampridine, dalfampridine, and related compounds represent potential therapeutic approaches for channelopathies involving this gene.