The human genome encodes 5 different KCNQ potassium channels, four of which are mutated in human inherited disease. Dominant negative mutations in KCNQ1 cause cardiac arrhythmia, whereas a total loss of KCNQ1 funtion as observed with recessive mutations on both alleles cause cardiac arrhythmia and deafness. Mutations in either KCNQ2 or KCNQ3 can cause BFNC, a dominant form of neonatal epilepsy. KCNQ2 and KCNQ3 can assemble to heteromeric channels, although both are also functional as homooligomers. These channels, as well as KCNQ4 and KCNQ5, have properties of the M-current. This K current is active at the threshold of action potential firing and regulates neuronal excitability. Mutations in KCNQ4, which is expressed in sensory outer hair cells (OHCs) of the organ of Corti and in the brainstem, underly a form of human dominant hearing loss. We have recently generated a KCNQ4 KO mouse and a knock-in mouse that carries a dominant negative mutation found in human patients. Both mouse strains develop deafness, with a time course that is slower with mice heterozgyous for the dominant mutation. The hearing loss can be correlated with a degeneration of OHCs. Inner hair cells, by contrast, remain intact. Patch-clamp analysis revealed a depolarization of OHCs by about 15 mV. These studies also identified KCNQ4 as the molecular correlate of the Ikn current of OHCs.