Studying how GPCR oligomers assemble with their signaling partners and traffic to the plasma membrane will certainly aid in understanding the specificity of signal transduction. Inefficient targeting of GPCR oligomers in vivo has been shown to be the cause of some pathophysiological disease states, emphasizing the importance of proper receptor assembly and trafficking towards plasma membrane. This study is among the first in attempting to understand how oligomerization of GPCRs is performed and/or regulated. Our work demonstrates that molecular chaperones will display levels of selectivity towards some receptor complexes, and that some chaperones will be involved in the formation of receptor oligomers. Also, the association of oligomers with their cognate signaling partners, such as G proteins may also very well be regulated by molecular chaperones. Our screen for molecular interactors of chemokine receptors has lead us to the identification of DRiP78, a member of the HSP40 protein family. Up to now, several GPCRs, including the D1-dopamine, M2-Muscarinic, A1-Adenosine, D2-dopamine and b2-adrenergic receptors have been shown to have the ability to interact with DRiP78, and in most cases, can be retained by the chaperone in ER Z-VAD-FMK membranes. Those receptors share the common reported DRiP78-recognition sequence within the receptor proximal c-tail. The chemokine receptors CXCR4 and CCR5 share part of this sequence, which appears to be sufficient for DRiP78 to interact. Indeed, CXCR4 and CCR5 do not possess the last phenylalanine residue shown in the recognition sequence, and rather possess solely the F4F portion. Small regions of the c-tail could therefore act as conformational switches, which upon masking or revealing would allow proper exit from the ER. As demonstrate by our study, DRiP78 can regulate receptor expression to the plasma membrane of WT receptors. DRiP78 could likely interact with CCR5 and mask the ER exit motif, therefore retaining the receptors inside the ER. The reciprocal also exists, as exemplified by the association of GABABR1 with GABABR2, which allows the heterodimeric complex to be released from the ER and reach the plasma membrane. Therefore, DRiP78 could likely act as a quality control checkpoint, assuring that receptors are properly folded and most likely assembled into competent oligomers with their signaling partners. Other chaperones, such as RTP4, were shown to promote cell surface expression, rather than ER retention and trafficking towards cell surface. RTP4 also appeared to be involved in the specificity of signaling complexes assembled, as it regulated the proportion of m-d heterodimers, and thus representing a critical factor influencing the signal transduction induced by exogenous and endogenous ligands. In terms of specificity, the bovine analog of DRiP78, Jiv, is essential for the polyprotein cleavage and replication of the pestivirus BVDB. Therefore, a role in the maturation of mammalian proteins like GPCRs could be possible.