ARHGEF12 acts as a guanine nucleotide exchange factor (GEF) for the RhoA GTPase. GEFs promote the exchange of GDP for GTP on Rho proteins, switching them into their active state. UniProt annotation also indicates that ARHGEF12 may act as a GTPase-activating protein (GAP) for GNA12 and GNA13, and that it may take part in the regulation of RhoA by the guanine nucleotide-binding alpha-12 and alpha-13 subunits. In endothelial cells, it promotes cell and actin stress fibre reorientation in response to mechanotransduction.

The ARHGEF12 gene encodes a protein classed by HGNC within the Dbl family Rho GEFs and among PDZ domain containing proteins. The protein is found in the cytoplasm and at membranes. Rho GTPases play a fundamental role in numerous cellular processes initiated by extracellular stimuli acting through G protein-coupled receptors, and the encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. The mouse ortholog is Arhgef12. Three transcript variants encoding different isoforms have been described for the human gene.

The protein is known by the alias LARG, and the older symbol KIAA0382 also appears in the literature. The approved name was formerly written as Rho guanine nucleotide exchange factor (GEF) 12. ARHGEF12 has been observed as a myeloid/lymphoid fusion partner in acute myeloid leukaemia, which has made it a point of interest in studies of Rho signalling in disease.