Asporin is an extracellular matrix protein that belongs to the small leucine-rich repeat proteoglycan (SLRP) family of proteins. It is unique among SLRPs in that it lacks a glycosaminoglycan attachment site and contains an asparatic acid (D) repeat at its amino terminus. Its biological role has been unclear, but recent genetic studies have demonstrated association between asporin and various bone and joint diseases, including osteoarthritis, rheumatoid arthritis and lumbar disc disease. Each of these common diseases presents a substantial medical, social and economical burden to societies worldwide. This paper reviews recent progress in the study of asporin, focusing on its expression, regulation and function as well as its role in the molecular pathogenesis of common bone and joint diseases. Asporin is found primarily in regions surrounding skeletal tissue and is up-regulated in disease states. It binds to various growth factors, including TGF-β and BMP-2, and negatively regulates their activity. By inhibiting binding of TGF-β1 to its type II receptor, asporin forms a functional feedback loop with TGF-β1 and regulates its chondrogenic potential. As an extracellular, tissue-specific protein, asporin represents a promising target for phamacogenomic approaches to common bone and joint diseases.