Abstract: Adenosine diphosphate ribosylation factors (ARFs) are small GTP-binding proteins of the Ras superfamily which are involved in membrane trafficking and actin cytoskeleton remodeling. Like other small GTPases, their functions are attributed to the cycling of ARF between GTP (active) and GDP (inactive) states through the actions of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins, respectively. Cytohesins are a GEF subfamily of ARFs in mammals with four members, namely, cytohesin-1, -2, -3, and -4.