The transient outward current (Ito) that mediates early (phase 1) repolarization is conducted by theKCND3-V392I was identified in an 18-year-old male with J wave syndrome/early repolarization syndrome, and a history of cardiac arrest including ventricular tachycardia/ventricular fibrillation and atrial fibrillation/atrial flutter. PathogenicKCND3-V392I demonstrated a marked gain-of-function phenotype, increasing peak IThis preclinical study provides pharmacological and functional evidence to suggest that Acacetin may be a novel therapeutic for patients with KCND3 gain-of-function-associated J wave syndrome by inhibiting I