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Matrilins (MATNs) are a family of non-collagenous extra-cellular matrix (ECM) proteins consisting of four known members that have been proposed to play key roles in modulating cellular phenotypes during chondrogenesis of mesenchymal stem cells (MSCs). MATN1 and MATN3 are expressed specifically in cartilage and are among the most up-regulated ECM proteins during chondrogenesis. MATN3 is composed of a single N-terminal von Willebrand Factor A (vWFA) domain followed by four epidermal growth factor (EGF) repeats and a coiled-coil domain whereas MATN1 is composed of two vWFA domains separated by one EGF-like domain. MATN1 or MATN3 may play a role in modulating chondrogenesis during the chondrocyte differentiation process. Mutations of this gene have been associated with variety of inherited chondrodysplasias. Recent studies show that aberrant expression and processing of MATN3 are hallmarks of conventional cartilaginous neoplasms.