The Rho family of small GTPase proteins comprises CDC42 (Cell Division Cycle-42), Rac, and Rho. Proteins of the Rho/Rac subfamily (Rho proteins) of small GTP-binding proteins function as molecular switches that regulate a multitude of biological processes including cell proliferation, apoptosis, differentiation, migration, cytoskeletal reorganization, and membrane trafficking. Like most of the Ras-related proteins, Rho GTPases cycle between an inactive GDP-bound conformation and an active GTP- bound conformation. Cycling between the two conformations enables these proteins to act as binary switches (Ref.1). The tightly regulated GTP-binding/GTPase cycle requires the coordinated action of three regulatory proteins: 1) GEFs (Guanine Nucleotide Exchange Factors), which stimulate the GTP–GDP exchange reaction; (2) GAPs (GTPase-Activating Proteins), which stimulate the GTP-hydrolytic reaction; and (3) GDIs (Guanine Nucleotide Dissociation Inhibitors), which antagonize the [...]