The K⁺ voltage-gated channel subfamily E member (KCNE) family is a group of small, non-conducting, single transmembrane domain proteins that associate with pore-forming potassium channel subunits to form mixed complexes with unique characteristics¹.

Five different KCNE proteins have been described (KCNE1-5)². The KCNE regulatory subunits are small proteins (14-20 kD) with a type-1 integral membrane topology. It is believed that both the cytoplasmic C-terminus tail and the transmembrane domain are necessary for the interaction with the α subunits¹.

MinK-related peptides (MiRPs) MiRP3, protein encoded by KCNE4³. The importance of these proteins to normal physiology of the heart and nervous system is exposed by their association with clinical disorders such as congenital long QT syndrome, drug-induced cardiac arrhythmias, sensorineural deafness, and periodic paralysis⁴. In addition, MiRPs influence the normal physiology of endocrine and exocrine glands, intestinal secretion, and renal excretion. MiRP3 is found to co-localize with K_V4.2 subunits that contribute to cardiac transient outward K⁺ currents⁵. Levels of the KCNE4 transcript in human cardiac ventricle are robust and increase in patients with congestive failure suggesting a regulatory function for MiRP3 in the heart⁶. In addition to regulating K_V4.2, MiRP3 also regulates KCNQ1 and BK channels^2,5.