KCNQ1 is a voltage-activated potassium channel alpha-subunit expressed in various cell types, including cardiac myocytes and epithelial cells. KCNQ1 associates with different beta-subunits of the KCNE protein family. In the human heart, KCNQ1 associates with KCNE1 to generate the IKs current characterized by its slow activation and deactivation kinetics. Mutations in either KCNQ1 or KCNE1 are responsible for at least four channelopathies that lead to cardiac dysfunction and one that leads to congenital deafness: the Romano-Ward syndrome, the short QT syndrome, atrial fibrillation, and the Jervell and Lange-Nielsen syndrome (cardioauditory syndrome). To date, nearly 100 different KCNQ1 mutations have been reported as responsible for the cardiac long QT syndrome, characterized by prolonged QT interval, syncopes, and sudden death. Patch clamp and immunofluorescence techniques are instrumental for characterization of the molecular mechanisms responsible for the altered function of KCNQ1 and its partners.