While it’s well established that elevated NHE1 activity plays a crucial role in heart failure, a potentially significant component of this indication is that NHE1 could activate pro-hypertrophic kinases, including Akt, extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p90 ribosomal protein S6 kinase (p90RSK). This evidence concerns the gene MAPK3 and heart failure.