In the asialoglycoprotein receptor (ASGPR¹) endocytic pathway, internalized receptors pass through early, recycling and sorting endosomal compartments before returning to the cell surface. Sorting motifs in the cytoplasmic domain (CD) and protein interactions with these sequences presumably direct receptor trafficking. Previous studies showed that association of a potential sorting heat shock protein (HSP) heterocomplex with the ASGPR- CD was regulated by Casein Kinase 2 (CK2) mediated phosphorylation. Mass spectrometry and immunoblot analyses identified five of these ASGPR-CD associated proteins as the molecular chaperones gp96, HSP70, HSP90, Cyclophilin-A and FKBP. The present study was undertaken to determine whether any of the adaptor protein complexes (AP1, AP2 or AP3) were selectivity associated with the ASGPR-CD. In conjunction with molecular chaperones, AP2 and AP1 were recovered from a CK2 phosphorylated agarose-GSH-GST-ASGPR-CD matrix. Binding of AP3 was independent of the phosphorylation status of the CD matrix. Inhibition of CK2 mediated phosphorylation with tetrabromobenzotriazole prevented AP recovery within an immunoadsorbed ASGPR complex. Rapamycin, which dissociates the HSP-heterocomplex from ASGPR-CD thereby altering receptor trafficking also, inhibited AP association. Similar results were obtained with the inhibitor of HSP90 heterocomplex formation, geldanmycin. The data presented provide evidence that recruitment of AP1 and AP2 necessary for appropriate receptor trafficking is mediated by the interaction of AP with the ASGPR-CD bound HSP complex.