<p>Ventricular arrhythmias following myocardial infarction (MI) remain a leading cause of sudden cardiac death, yet therapeutic options are limited by incomplete understanding of the molecular mechanisms governing post-infarction arrhythmogenesis. While RNA-binding proteins have emerged as critical regulators of cardiovascular pathophysiology, their role in cardiac electrophysiology remains largely unexplored. Here, we demonstrate that cold- inducible RNA-binding protein (CIRP) functions as a critical regulator of ventricular arrhythmia susceptibility through post-transcriptional control of cardiac ion channels. In a rat MI model, cardiac-specific CIRP overexpression was achieved using AAV9 gene delivery under cTNT promoter control, followed by LAD ligation. Our results show that CIRP gene therapy significantly reduced ventricular arrhythmia inducibility in programmed electrical stimulation studies and improved cardiac function parameters. Electrophysiological analysis revealed that CIRP prolonged action potential duration through selective post-transcriptional downregulation of Kv4.2 and Kv4.3 potassium channel proteins without altering mRNA levels. This post-transcriptional mechanism represents a novel pathway linking temperature-responsive RNA regulation to electrophysiological stability. Western blot and RT-PCR analysis confirmed protein-specific suppression of target ion channels in CIRP-treated hearts. These results establish CIRP as a critical mediator in the post-transcriptional regulatory network governing cardiac rhythm and identify RNA-binding protein modulation as a promising therapeutic strategy for post-MI arrhythmia prevention. This mechanistic insight opens new avenues for understanding how cellular stress responses influence cardiac electrophysiology and may inform the development of next-generation antiarrhythmic therapies.</p> Graphical Abstract <p></p>