KCNE1 is a regulatory beta subunit that modulates voltage-gated potassium (Kv) channel function, with critical roles in cardiac electrophysiology. It primarily associates with KCNQ1 alpha subunits to form the slowly activating delayed rectifier cardiac potassium (IKs) channel essential for ventricular muscle action potential repolarization 1. KCNE1 enhances channel stability and modulates gating kinetics 2, with steady-state outward current reaching completion after approximately 50 seconds 1. The subunit also modulates delayed rectifier Kv channels containing KCNB1 2 and may regulate rapidly activating components of the delayed rectifying potassium current through KCNH2/HERG association 3. KCNE1 mutations cause Long QT syndrome 5 (LQT5) and Jervell and Lange-Nielsen syndrome 2, accounting for approximately 1-3% of identified LQTS mutations in clinical populations 456. The G38S polymorphism significantly increases atrial fibrillation risk across multiple populations 7. In contrast, KCNE1 variants show no significant association with Ménière's disease risk 8. KCNE1 and KCNE3 produce opposite regulatory effects on KCNQ1, with KCNE1 creating slowly-activating channels critical for cardiac repolarization 9, making KCNE1 dysfunction clinically significant for sudden cardiac death prevention.