Members of the Rho (or ARH) protein family and other Ras-related small GTP-binding proteins are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. At least 3 classes of proteins tightly regulate cycling between the GTP-bound and GDP-bound states: GTPase-activating proteins (GAPs); guanine nucleotide-releasing factors (GRFs), and GDP-dissociation inhibitors (GDIs). The GDIs decrease the rate of GDP dissociation from Ras-like GTPases. ARHGDIB was expressed abundantly in lung, and at lower levels in several other tissues. Overexpression of ARHGDIB in mammalian cells caused them to 'round up' and disrupted the actin cytoskeleton, mimicking the phenotypic changes associated with inactivation of Rho proteins.