Conversely, constitutive activation of PKA in cardiomyocytes causes a severe heart failure phenotype (67), suggesting alternative strategies to repress or antagonize PKA activity, such as enhancement of Rac1 S-palmitoylation or PR72-regulated phosphatase activity, could provide a more targeted means to repress pathogenic PKA activity and diminish cardiac hypertrophy and decompensation in response to sustained β-adrenergic signaling (Figure 9) without the untoward side effects of beta blockers or substantial cAMP-dependent effects on heart rate and conduction velocity. The gene discussed is RAC1; the disease is heart failure.