RhoGDIβ is implicated in cancer progression, however, reports have presented contradictory evidence as to the nature of the correlation between cancer progression and RhoGDIβ expression level [44]. We have also reported that RhoGDIβ plays a positive [41,45,46] and negative [47] role in cancer progression. Several explanations for this contradictory behavior of RhoGDIβ have been proposed [44]. Our present study suggests that RhoGDI can act both as a positive and negative regulator of GTPases, and which role RhoGDI plays may depend on its expression level. This presents at least a partial explanation for the inconsistent correlation of RhoGDIβ with cancer progression.