To examine the role of S-palmitoylation of Rac1 in cardiomyocyte stress-responsive signaling and cardiac hypertrophy in vivo, we generated conditional knockin mice with cardiomyocyte-specific mutation of the Cys-178 palmitoylation site (Rac1cKI) and subjected them to several models of chronic pathological hypertrophic stress to evaluate their propensity for the development of heart failure. The gene discussed is RAC1; the disease is heart failure.