For example, Brugada syndrome, a potentially lethal cardiac rhythm disturbance, can be caused by increased ventricular Ito resulting from gain-of-function mutations not only in KCND3 (which encodes Kv4.3; Giudicessi et al., 2011), but also in KCNE3 (Delpon et al., 2008) and KCNE5 (Ohno et al., 2011). Here, KCND3 is linked to Brugada syndrome.