The Ras superfamily of small GTP-binding proteins are critical mediators of diverse cell signaling pathways, including those leading to proliferation, cytoskeletal organization and secretion. The counter-conversion of the active GTPbound form of these proteins to their inactive GDP-bound form is influenced by two types of regulatory proteins: those that alter the intrinsic GTPase activity of the GTP-binding proteins and those that alter the rate of GDP/GTP exchange. Guanine nucleotide-releasing factors (GRFs) increase the GDP dissociation rate, while GDP-dissociation inhibitors (GDIs) decrease the dissociation rate. The Rho GDI subfamily is composed of Rho GDI?, Ly-GDI (also known as Rho GDI? and previously known as GDI/D4) and Rho GDI?. The Rho GDI proteins interact with and have varying affinities for several Ras-like GTP binding proteins, including Rho A, Rho B, Rac and Cdc42. Ly-GDI is expressed only in hematopoietic cells, predominantly in B and T lymphocyte cell lines.