GEFs catalyze the release of GDP from inactive Ras proteins to ena-ble GTP binding. Lfc (also designated Rho/Rac guanine nucleotide exchange factor 2, lymphoid blast crisis-like 1, ARHGEF2, GEF-H1, KIAA0651 or LFP40) is an 894 amino acid GEF for Rho A, a member of the Ras family that regulates the Actin cytoskeleton during the formation of stress fibers. Lfc directly interacts with Cingulin, a junctional adapter that inhibits Rho A, thus preventing phorbol-12-myristate-13-acetate-induced contraction and apoptosis. Mutations in the p53 gene transcriptionally activate Lfc, thereby increasing tumor cell proliferation.