The ADP-ribosylation factor (ARF) protein family are structurally and functionally conserved members of the Ras superfamily of regulatory GTP-binding proteins. ARFs influence vesicle trafficking and signal transduction in eukaryotic cells. ARF6 plays a role in protein trafficking near the plasma membrane, including receptor recycling, cell adhesion and cell migration. ARF6 colocalizes with the ARF guanine nucleotide-exchange protein (GEP) BRAG2, also designated GEP100. BRAG2 is ubiquitously expressed as two isoforms, BRAG2a and BRAG2b, which can cycle between the cytoplasm and the nucleus. BRAG2, via its interaction with ARF6, is involved in the regulation of cell adhesion by controlling Integrin ∫1 endocytosis and E-cadherin redistribution. BRAG2 has also been shown to bind directly to Tyr1068/1086-phosphorylated EGFR to activate ARF6, which induces tumor invasion in MCF7 cells. Therefore, BRAG2 may contribute to the metastasis and malignancy of some breast cancer cells.