Various hormones (Ang II, aldosterone) released during HF or myocardial ischemia (MI) can activate NHE1, inhibit NCX, and lead to intracellular calcium overload, which in turn activates NHE1 and exacerbates calcium overload (Figure 1A) (Kim et al., 2017). The gene discussed is SLC9A1; the disease is myocardial infarction.