Matrilin (MATNs) are a family of non-collagenous extracellular matrix proteins consisting of four known members that have been proposed to play key roles in the formation of both collagen-dependent and collagen-independent filamentous networks. The matrilin family all share a structure made up of von Willebrand factor A domains, epidermal growth factor-like domains and a coiled coil alpha-helical module. MATN1 and MATN3 are expressed mainly in cartilage, while MATN2 and MATN4 occur in a wide variety of extracellular matrices. The matrilin genes are strictly and differently regulated and their expression may serve as markers for cellular differentiation and diseases such as astrocytoma and liver carcinoma. Recent studies show that MATN2 is a permissive substrate for axonal growth and cell migration, and it is required for successful nerve regeneration.