KCNE3 (or MiRP2) is a member of a family of proteins that regulate the activity of voltage-dependent K⁺ channels. Other members of the family are KCNE1 (IsK, MiNK), KCNE2 (MiRP1), KCNE4 (MiRP3) and KCNE5 (MiRP4).

KCNE1 is the founding member of the family and was initially believed to form a K⁺ channel itself, but was later recognized to work as a regulatory b subunit associated with the K_V7.1 (KCNQ1) a protein. KCNE3 was discovered based on its homology with KCNE¹.

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 a subunits. The stoichiometry of the KCNE subunits with their partner a subunits in the native channels is not clear and ratios ranging from 2 to 14 KCNE subunits per 4 a subunits have been proposed.

KCNE3 is relatively widely expressed in several tissues with prominent expression in the kidney and skeletal muscle.

KCNE3 is quite promiscuous and associations with K_V7.1, K_V3.4, K_V7.4 (KCNQ4), K_V11.1 (HERG), K_V2.1 and K_V3.1b have been demonstrated. The best characterized interactions are with the former two proteins. KCNE3 interacts with K_V7.1 in epithelial cells of the gastrointestinal tract where it appears to be important for Na⁺ absorption. In skeletal muscle, KCNE3 couples to K_V3.4 to regulate muscle function. Indeed, a mutation in KCNE3 (R83H) has been associated with an inherited form of periodic paralysis (Thyrotoxic hypokalemic periodic paralysis).