Regulation of the Balance between Concentric and Eccentric Cardiac Hypertrophy by a CDC14A-KMT5A Signaling Pathway

<b>What is new:</b> A function is identified for the first time for the protein phosphatase CDC14A in the heart, regulation of cardiomyocyte morphology and overall cardiac geometry in pathological cardiac remodeling.The lysine methyltransferase KMT5A is shown to mediate the effects of CDC14A in the adult cardiomyocyte by regulating H4K20 mono-methylation, such that reduced KMT5A expression promotes a phenotype resembling Dilated Cardiomyopathy.H4K20me1 epigenomic modification is identified as a regulator of cardiac structure and function.<b>Clinical implications:</b> CDC14A loss of function experimentation <i>in vivo</i> , resulting in improved cardiac structure and function in a mouse model of Dilated Cardiomyopathy, suggests that CDC14A is a novel therapeutic target for heart failure with reduced ejection fraction.