By analyzing expression profiles of human mesenchymal stem cells incubated in osteogenic supplements, we identified and characterized a novel human cDNA, elastin microfibril interface located protein-5 (EMILIN-5), that is likely to play a significant role in the process of osteogenesis. The deduced EMILIN-5 product consists of 766 amino acids with a cysteine-rich EMI domain at the NH2 terminus. Western blotting detected EMILIN-5 expression in a variety of osteoblastic cell lines. Immunohistochemistry of mouse embryos 13.5 days post-coitus revealed relatively high levels of EMILIN-5 protein in perichondrium cells of developing limbs. Our findings suggest that the EMILIN-5 gene plays an important role in skeletal development. (C) 2003 Elsevier Inc. All rights reserved.