EGFR and heart failure: From the perspective of the MR regulating downstream GPCRs and GPCR signaling mediators/regulators (Figure 1), therapeutic targeting of proteins directly activated by aldosterone like GPER, EGFR, and PKC has the potential of combating several non-genomic actions of aldosterone, which are as deleterious for the myocardium as its classic genomic actions, e.g., EGFR transactivation-mediated fibrosis, PKC-mediated hypertrophy, etc. Targeting of several of these signaling mediators is already being pursued for heart failure therapy, independently of their molecular connections with the cardiac MR.