The discrepancy between the effect of HIPK2 in the Guo et al. study, where HIPK2 is found to be reduced in human end-stage ischemic cardiomyopathy [114], and in the Zhou et al. study, where HIPK2 is overexpressed in cardiomyocytes of a TAC model [105], could depend on different molecular strategies for generating HIPK2-/- mice, or by the fact that the protective effect of HIPK2 knockdown was only found in stressed conditions [105]. Here, HIPK2 is linked to ischemic cardiomyopathy.