Potassium voltage-gated channel subfamily E regulatory subunit 5 (KCNE5)

Potassium voltage-gated channel subfamily E regulatory subunit 5 (KCNE5) is a single-pass transmembrane protein that acts as an auxiliary, non-pore-forming subunit for voltage-gated potassium channels, especially in the heart. KCNE5 modulates the function of pore-forming Kv alpha subunits, particularly KCNQ1, and alters the biophysical properties of the channel complex, including ion selectivity, gating kinetics, and voltage dependence. KCNE5 generally inhibits or fine-tunes the slowly activating delayed rectifier potassium current (IKs), which is crucial for cardiac repolarization and rhythm stability. Genetic variants or mutations in KCNE5 are associated with arrhythmogenic cardiac disorders such as atrial fibrillation, Brugada syndrome, and idiopathic ventricular fibrillation. KCNE5 does not directly conduct ions but profoundly influences the physiological and pathophysiological function of Kv channels, and therefore, impacts cardiovascular electrophysiology. It is encoded by an X-linked gene and is among the less-studied members of the KCNE family, but its role in cardiac health is increasingly recognized.

Other names

Potassium channel subunit beta MiRP4AMMECR2KCNE1LAMME syndrome candidate gene 2 proteinKCNE1-likecardiac voltage-gated potassium channel accessory subunit 5potassium voltage-gated channel subfamily E member 1-like proteinIsk-related family member 1-like

Not applicable for direct drugs; however, KCNE5 modulates Kv channel activity, especially KCNQ1-dependent currents. Mutations or altered subunit expression can impact channel pharmacodynamics and downstream effects of antiarrhythmic drugs.