Sustained activation of the signaling pathways driven by calcium-calmodulin dependent protein kinase II (CaMKII) appear to play a central role as a determinant of cardiomyocyte remodeling and dysfunction in HCM myocardium (Figure 3), as observed in several human and animal models of cardiac hypertrophy and heart failure (Ling et al., 2009; Toischer et al., 2010; Fischer et al., 2013). The gene discussed is CAMK2G; the disease is cardiac hypertrophy.