These data collectively suggest a working hypothesis whereby zDHHC3 activity at the cardiomyocyte Golgi S-palmitoylates Rac1 to promote its sarcolemmal translocation and signaling activity along with induction of all small GTPases of the Rho family and RhoGDI, which is associated with congestive heart failure in zDHHC3 transgenic mice that also phenocopies cardiac-specific overexpression of RhoA or Rac1 (10, 21). The gene discussed is RHOA; the disease is congestive heart failure.