The final developed NOPT peptide (16-mer), substituted with an N-methyl proline, showed a 17-fold increased stability in human serum compared with OPT, precipitated endogenous PLM from left ventricle lysate, exhibited a direct pSer68-PLM binding, outcompeted the direct PLMcyt-NCX1cyt interaction and increased endogenous NCX1 activity when it was introduced as a cell-permeable peptide into adult cardiomyocytes that were isolated from SHAM-operated and aorta banded HF mice. This evidence concerns the gene FXYD1 and hydrops fetalis.