Previously, by comparing the cellular processes in which RKIP is implied and by analyzing the function of numerous molecular partners, we have suggested that RKIP may participate in regulating actin reorganization and membrane remodeling. Here, based on the role of RKIP in cancer, we describe the cellular function of five important partners of RKIP (GRK2, IQGAP, MT1-MMP, LC3 and Rab8). By their own activity, they may explain, at least in part, the multiple functions of RKIP as they are key actors in diverse cellular processes. All these proteins play a role in the formation or maturation of cellular protrusions such primary cilium, lamellipodia, filopodia or invadopodia. Considering the close relationship between actin cytoskeleton and membrane during cell migration, we suggest that a major role of RKIP in cells is likely to associate with main molecular assemblies, in order to drive the cortical actin/membrane complex in response to signaling pathways. In cancer cells, because of the lack of RKIP, this important regulation is lost.