The Ras p21 family of guanine nucleotide proteins has been widely studied in view of its role in signal transduction pathways and high frequency of mutations in human malignancies. The founding members of the Ras family (H-, K- and N-Ras p21) are members of a much larger superfamily of related proteins. Six members of this family, Rap 1A, Rap 1B, Rap 2, R-Ras, Ral A and Ral B, exhibit approximately 50% amino acid homology to Ras. The mammalian Rho proteins (Rho A, B, C, 6, 7 and 8) are approximately 30% homologous to Ras and are expressed in a wide range of cell types. Three Rho-related GTPases Rnd1 (Rho 6), Rnd2 (Rho 7), and Rnd3 (Rho 8 or Rho E) form a distinct branch of the Rho family since they differ from other Rho proteins in size, charge, and biochemical properties.