The current study identifies KLF15 as a causative gene contributing to AF as well as ventricular arrhythmias and hypertrophic cardiomyopathy, which provides novel insight into the molecular pathogenesis of cardiac arrhythmias and cardiomyopathy, with potential implications for genetic counseling and individualized prophylaxis for cardiac arrhythmias and cardiomyopathy in a subset of patients. Here, KLF15 is linked to hypertrophic cardiomyopathy.