KCNE5 is an X-linked ancillary subunit of voltage-gated potassium channels that modulates cardiac repolarization 1. As a beta-subunit, KCNE5 forms heteromeric complexes with alpha-pore-forming Kv channel subunits, most notably KCNQ1, where it induces time- and voltage-dependent modulation of potassium currents 2. KCNE5 shifts the KCNQ1 activation curve positively by >140 mV and regulates delayed rectifier potassium current (IKs) kinetics at physiological temperatures 2. KCNE5 also interacts with KV2.1 at intercalated discs, controlling its intracellular localization and ventricular outward potassium currents 3. Mutations in KCNE5 are associated with cardiac arrhythmias including atrial fibrillation and Brugada syndrome 13. The AF-associated L65F mutation causes a gain-of-function in IKs by abolishing KCNE5's normal current-suppressing effect 4. In mice, Kcne5 deletion increases ventricular potassium current density and susceptibility to polymorphic ventricular tachycardia 3. Notably, KCNE5 mutations were not identified in a large long QT syndrome cohort, suggesting limited involvement in congenital LQTS 5. KCNE5 is also expressed in placental tissue, where it may regulate vascular reactivity during fetal development 6.