To directly examine the hypothesis that Zdhhc3 overexpression in the heart drives hypertrophy and cardiomyopathy through Rac1 signaling induction, we utilized Rac1-loxP-targeted (Rac1f/f) mice crossed with αMHC promoter–driven Cre transgenic animals to establish a cardiomyocyte-specific deletion of Rac1 in the heart with zDHHC3 overexpression (DTgZdhhc3 Rac1f/f-αMHCcre). The gene discussed is ZDHHC3; the disease is cardiomyopathy.