Rho GTPases, which play fundamental roles in numerous cellular processes, are initiated by external stimuli that signal though G-protein coupled receptors. ARHGEF5 (Rho guanine nucleotide exchange factor (GEF) 5), also known as P60 or transforming immortalized mammary oncogene (TIM), is a 1597 amino acid cytoplasmic protein. ARHGEF5 is believed to form a complex with G proteins and be involved in the initiation of Rho-dependent signals. It has also been suggested that ARHGEF5 may be involved in the organization of the cytoskeleton. ARHGEF5 contains one PH domain, one DH domain and one SH3 domain. Existing as two isoforms produced by alternative splicing, ARHGEF5 is mainly expressed in pancreas, liver, kidney, placenta and lung.