Members of the large aggregating chondroitin sulfate proteoglycans are characterized by anN-terminal fragment known as G1 domain, which is composed of an immunoglobulin (IgG)-like motifand two tandem repeats (TR). Previous studies have indicated that the expressed product of aggrecan G1domain was not secreted. Here we demonstrated that the inability of G1 secretion was associated with thetandem repeats but not the IgG-like motif, and specifically with TR1 of aggrecan. We also demonstratedthat the G2 domain, a domain unique to aggrecan, had a similar effect on product secretion. The sequenceof TR1 of G1 is highly conserved across species, which suggested similar functions played by thesemotifs. In a yeast two-hybrid assay, TR1 interacted with the calcium homeostasis endoplasmic reticulumprotein. Deletion/mutation experiments indicated that the N-terminal fragment of TR1, in particular, theamino acids H2R4 of this motif were key to its effect on product secretion. However, the N-terminal 55amino acids were required to exert this function. Taken together, our study suggests a possible molecularmechanism for the function of the tandem repeats in product processing.