Osteopontin, also known as secreted phosphoprotein 1 (SPP1) and early T lymphocytes activation 1 (ETA-1), is an arginine-glycine-aspartic acid (RGD) that contains multi-functional glycoproteins who are able to interact with integrins and CD44 as receptors. This protein has been shown to play roles in cell migration and survival, bone remodeling, regulation of immune cell functions, apoptosis, control of tumor cell phenotypes, and autoimmune diseases. Osteopontin is involved in recruiting and stimulating macrophages and lymphocytes in response to microbial infections. The Osteopontin receptor-ligand interaction mediates chemotaxis or attachment that depends on whether the protein is in soluble or immobilized form. Osteopontin has also been shown to play a role in the progression of cancer, which is supported by the finding that patients who suffer from disseminated carcinoma also have increased levels of Osteopontin in their plasma. In addition, Osteopontin is a component of the human atherosclerotic plaque and may be a mediator of arterial neointima formation. It is synthesized by macrophage, smooth muscle, and endothelial cells in primary and recurrent human coronary atherosclerotic plaques, which may contribute to the cellular accumulations and dystrophic calcification in the atherosclerotic plaques. Osteopontin is also a substrate for MMP-3, MMP-7, MMP-9, MMP-12, and thrombin within the SVVYGLR motif.