In contrast to cardioprotective GRK2 inhibition with kinase-inactive GRK2-K220R, transgenic expression of the dual-specific GRK2 and Raf-Erk1/2 axis inhibitor, RKIP, promoted signs of heart failure, i.e., cardiac hypertrophy, cardiac dilatation and cardiotoxic lipid load. This evidence concerns the gene RAF1 and heart failure.