KCNK18 encodes TRESK, a two-pore domain potassium channel that conducts voltage-dependent outward and inward rectifying currents at depolarized and hyperpolarized membrane potentials, respectively 123456. The channel forms homo- and heterodimers with distinct regulatory properties. In trigeminal sensory neurons, KCNK18 heterodimers stabilize resting membrane potential and regulate action potential threshold and spike frequency, thereby inhibiting neuronal firing and neurogenic inflammation. In thymocytes, KCNK18 conducts K+ currents upon T cell receptor signaling, promoting sustained Ca2+ influx and NF-κB activation to facilitate regulatory T cell differentiation 7. KCNK18 variants are implicated in migraine pathogenesis, with mutations identified in both familial hemiplegic migraine and common migraine forms 891011. An Italian cohort study identified multiple genetic variants (R10G, C110R, S231P, F372L) in 5.1% of migraine with aura and 7.1% of migraine without aura patients; in silico analysis suggested some variants have potentially damaging effects on channel function 12. Zebrafish modeling demonstrated that K2P18.1 channels stabilize resting membrane potential through K+-selective background currents and share regulatory properties with the human ortholog 13. Recent evidence expands KCNK18's clinical relevance beyond migraine to neurodevelopmental disorders, with biallelic variants associated with intellectual disability and autism spectrum disorder 14. KCNK18 variants were also detected in both painful and painless diabetic neuropathy patients, though their causal role remains unclear 15.