ITFG2 is an intracellular protein known to modulate the immune response of T-cells. Our previous investigation revealed that ITFG2 specifically targets ATP5b to regulate ATP energy metabolism and maintain mitochondrial function, thereby protecting the heart from ischemic injury. However, the role of ITFG2 in ischemic ventricular arrhythmias and its underlying mechanisms have not been previously reported. In this study, we found ITFG2 overexpression, induced by an adeno-associated virus serotype 9 vector, partially reduced the incidence of ischemic ventricular arrhythmias and shortened the duration of ventricular arrhythmias in mice after myocardial infarction. Conversely, shRNA-mediated knockdown of endogenous ITFG2 aggravated ischemic ventricular arrhythmias. ITFG2 overexpression also shortened the prolonged QRS complex and increased the epicardial conduction velocity in MI mice. Additionally, the hearts from ITFG2 overexpression mice exhibited a higher maximal upstroke velocity at phase 0 of transmembrane action potential compared to MI mice. Patch-clamp analyses demonstrated a 50% increase in the peak current of voltage-dependent Na