Acts as a guanine nucleotide exchange factor (GEF) for RHOA and RHOC (PubMed:15107133, PubMed:26823019). Promotes actin stress fiber formation, force-induced stress fiber reinforcement and organization of KRT8/KRT18 networks via activation of RHOA/ROCK signaling, which is mediated by N-terminus KRT18 binding (PubMed:26823019, PubMed:30929300). Regulates the formation or maintenance of properly elongated morphology of epithelial tubules, via mediation of the organization and orientation of KRT18 filaments (By similarity). Promotes RHOA-dependent, cell-cell contact mediated reorientation of endothelial cells and their actin stress fibers in response to mechanotransduction (PubMed:25795300). Positively regulates hemidesmosome formation via acting as a linker protein that anchors keratin filaments to hemidesmosomes (PubMed:29672603). Also required for JUP localization at cell-cell adhesion junctions (PubMed:26823019). {ECO:0000250|UniProtKB:A0A8I3PMN2, ECO:0000269|PubMed:15107133, ECO:0000269|PubMed:25795300, ECO:0000269|PubMed:26823019, ECO:0000269|PubMed:29672603, ECO:0000269|PubMed:30929300}. This is the function of ENSG00000165801 (ARHGEF40, Rho guanine nucleotide exchange factor 40).