Handigodu disease is a disorder of osteoarticular system, specific to particular region viz shimoga and chickmagalore districts of Karnataka state, India. The present study focuses to understand the metabolism of aggrecan, a key glycoprotein of cartilage matrix in Handigodu Disease (HD) using serum specimen. The Dimethylmethylene Blue Chloride (DMB) dye was used to precipitate glycosaminoglycans (GAGs) associated proteins in serum. DMB dye was removed from GAGs associated proteins and electrophoresed on SDS-PAGE. The five GAGs associated protein bands were separated, among them two bands; 21.5 KDa and 55.4 KDa were immunoreactive to anti-human aggrecan antibody. These two GAGs associated protein bands were more dense (86% for 21.5 KDa and 61 % for 55.4 KDa) in affected group when compared to unaffected group in Handigodu Disease. These results may imply defective metabolism of aggrecan in a disease condition. The study needs to be extend for other arthritis / dysplastic bone disorders.