Previously, only matrix metalloproteinases were believed capable of cleaving the cartilage proteoglycan, aggrecan, between Asn(341) and Phe(342), to yield a small G1 fragment terminating in the residues VDIPEN. We show that the combined endo- and exopeptidase activities of the cysteine protease, cathepsin B, also generate this epitope, suggesting that it should no longer be considered as an exclusive marker of metalloproteinase activity.