Osteopontin (OPN) is in the small integrin-binding ligand N-linked glycoprotein (SIBLING) family. Osteopontin is a secreted matricellular cytokine with an important role in bone mass regulation. OPN is involved in osteoclast attachment to the mineralised bone matrix. The regulation of OPN is linked to the development of several bone-related diseases, including osteoporosis, rheumatoid arthritis, and osteosarcoma. It is a transformation-associated protein that binds to the integrin and CD44 cell membrane surface receptors. These receptors are correlated with biomineralisation, cell-mediated immunity, inflammation, fibrosis, as well as cell survival, tumorigenesis, and metastasis. OPN also has a role in cardiac health; acute increases can be protective, but chronic increases are linked to cardiovascular disease and other vascular diseases.