We work on the treatment of myocardial fibrosis. Progressive fibrosis results in myocardial stiffening and dysfunction in patients with heart failure contributing to ventricular remodeling and impaired contractility (Heart Failure with preserved Ejection Fraction, HFpEF). Despite the high global burden and intensive research, no therapies are available to remove excessive fibrosis and thus, induce reverse remodeling. The right (RV) and the left ventricle (LV) differ markedly in their embryonic development, anatomy and function. We found a potent anti-fibrotic capacity of the RV, but not the LV in reversible murine model of heart failure due to a preserved anti-fibrotic mechanism necessary for physiological postnatal adaptation. RNA sequencing revealed an undescribed gene as the underlying cause. We characterized the function of the gene in vitro and in vivo, and its role in postnatal physiological adaptation of the RV. We found a potent anti-fibrotic function of the gene. Our data reveal a so far undescribed gene as potential anti-fibrotic agent to treat myocardial fibrosis in heart failure. Currently, we are testing AAV-based and mRNA-based therapeutic strategies test its therapeutic efficacy in vivo.