KCNK17 encodes TASK-4, a two-pore domain potassium channel conducting voltage-dependent outward rectifying currents through an 'ion flux gating' mechanism where outward (but not inward) potassium flow opens the channel gate 1234. The channel forms homo- and heterodimers with distinct regulatory properties 4 and is permeable to monovalent cations including K+, Rb+, and Cs+ 3. In the cardiac system, KCNK17 is strongly expressed in Purkinje cells where it regulates action potential duration and conduction velocity 5. A gain-of-function mutation (p.Gly88Arg) increases channel conductivity and slows action potential upstroke in cardiac myocytes, contributing to conduction disorders 5. Inherited KCNK17 variants are associated with progressive cardiac conduction disorders 6. Genetically, KCNK17 variants correlate with cerebral hemorrhage risk in Chinese populations, with rs12214600 showing significant association after adjusting for age, sex, and hypertension 7. Additionally, KCNK17 expression is reduced in hepatocellular carcinoma and serves as a diagnostic/prognostic biomarker 8. A variant near KCNK17 (rs2815063) associates with cancer treatment-induced cardiac dysfunction in childhood cancer survivors, particularly those exposed to doxorubicin, through KCNK17 downregulation 9. KCNK17 also contributes to transcriptomic signatures predicting rheumatoid arthritis response to TNF inhibitor therapy 10.