Osteopontin (OPN) is a glycosylated phosphoprotein found in all body fluids and in the proteinaceous matrix of mineralized tissues. It can function both as a cell attachment protein and as a cytokine, delivering signals to cells via a number of receptors including several integrins and CD44. Expression of OPN is enhanced by a variety of toxicants, especially those that activate protein kinase C. In its capacity as a signaling molecule, OPN can modify gene expression and promote the migration of monocytes/macrophages up an OPN gradient. It has both inflammatory and anti-inflammatory actions. Some experiments suggest that it may inhibit apoptosis, possibly contributing to the survival of cells in response to toxicant injury. Elevated OPN expression often correlates with malignancy and has been shown to enhance the tumorigenic and/or metastatic phenotype of the cancer cell. Recent studies have revealed that OPN plays critical roles in bone remodeling and cell-mediated immunity.