RHOD is a RHO GTPase that possesses an elevated intrinsic guanine nucleotide exchange activity (Jaiswal, Fansa et al. 2013) and has never been shown to interact with any guanine nucleotide exchange factor (GEF) except with ARHGEF2 in a high-throughput study by Paul et al. 2017, although no activation of RHOD by ARHGEF2 was demonstrated. The following GEFs were specifically shown to not interact nor activate RHOD: DOCK11 (Ruiz-Lafuente et al. 2015), ITSN1 (Jaiswal et al. 2013), MCF2 (Jaiswal et al. 2013), MCF2L (Jaiswal et al. 2013), PREX1 (Jaiswal et al. 2013), TIAM1 (Jaiswal et al. 2013), TRIO (Jaiswal et al. 2013) and VAV2 (Jaiswal et al. 2013). As GTP is more abundant in cells than GDP (Traut 1994), RHOD is thought to be present in a constitutively active state (Jaiswal, Fansa et al. et al. 2013).
RHOD localization depends on its activation state - inactive RHOD is mainly cytosolic, while GTP-bound RHOD is found at the plasma membrane and at vesicle membranes (Blom et al. 2018).