KCNK9 (TASK-3) is a two-pore domain potassium channel that conducts voltage-dependent outward rectifying currents through 'ion flux gating,' where outward K+ flow opens the channel gate 12. The channel undergoes pH-dependent ion selectivity switching, becoming Na+-permeable upon extracellular acidification via protonation of His-98, which stabilizes C-type inactivation 3. KCNK9 forms homo- and heterodiomeric channels with distinct gating properties, regulating neuronal excitability by hyperpolarizing resting membrane potential while supporting high-frequency action potential firing in cerebellar and hippocampal granule neurons 4. The gene exhibits maternal-specific imprinted expression in brain tissue 5. Pathologically, KCNK9 is amplified 3-10 fold and overexpressed up to 100-fold in 44% of breast tumors, promoting tumor formation and resistance to hypoxia and serum deprivation 6. In melanoma cells, KCNK9 silencing causes mitochondrial depolarization and triggers caspase-dependent and -independent apoptosis 7. Antibody-mediated KCNK9 inhibition reduces carcinoma cell viability and suppresses xenograft growth and metastasis 8. Loss-of-function KCNK9 mutations cause KCNK9 imprinting syndrome, a neurodevelopmental disorder characterized by motor delay, intellectual disability, and hypotonia 9. The paternal allele near KCNK9 influences body mass index through parent-of-origin effects 10.