hERG (Kv11.1) is a voltage-gated potassium channel with important cardiovascular function. Many potential and marketed drugs bind to and inhibit hERG function, causing prolongation of the electrocardiogram QT interval, which leads to life-threatening ventricular arrhythmias. Understanding of hERG function is critical for drug discovery and development. hERG exhibits a unique bell-shaped current-voltage relationship which is a result of very rapid inactivation of the channel upon voltage activation. ICA-105574 is a small molecule activator of hERG that binds to the channel to remove inactivation, thereby increasing peak current amplitude and shortening the action potential. It also modulates activation kinetics of the channel. ICA-105574 differs in efficacy, mechanism of action, and/or binding site from other known hERG activators and enhancers. This compound is a valuable tool for furthering understanding of hERG biophysics and physiology, expecially the structural transitions that occur during inactivation.