Human IGF binding protein 4 (IGFBP-4) was isolated from human plasma based on its ability to bind immobilized IGF-I. Human IGFBP-4 cDNA encodes a 258 amino acid (aa) residue precursor protein with a predicted 21 aa residue signal peptide that is processed to generate the 237 aa residue mature human IGFBP-4. The human IGFBP-4 contains a potential N-linked glycosylation site and shares approximately 90% amino acid sequence identity with both the mouse and rat IGFBP-4. According to the nomenclature of IGFBPs defined at the 4th International Symposium of IGFs (1997, Tokyo), six high-affinity IGF binding proteins (IGFBP-1, -2, -3, -4, -5, -6), and four IGFBP-related proteins (IGFBPr-1, - 2, -3, -4) have now been identified. All IGFBPs have a high cysteine content and share conserved cysteine residues that are clustered in the amino- and carboxy-terminal thirds of the molecule. IGFBPs have been shown to either inhibit or enhance the biological activities of IGF, or act in an IGF-independent manner. Post-translational modification of IGFBPs, including phosphorylation and proteolysis, have been shown to modify the affinities of the binding proteins for IGF and may indirectly regulate IGF actions (Jones, J. I. and D.R. Clemons, 1995, Endocrine Rev. 16:3; Kelly, K.M. et al., 1996, Intl. J. Biochem. Cell Biol. 28:619 - 637; Kim, H-S. et al., 1997, Proc. Natl. Acad. Sci. USA 94:12981).