Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. Ligand for integrin alpha-V/beta-3. Bone. Found in plasma. Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers, increasing its collagen binding properties. Extensively phosphorylated by FAM20C in the extracellular medium at multiple sites within the S-x-E/pS motif (PubMed:15869464, PubMed:22582013, PubMed:26091039). The phosphorylated form inhibits hydroxyapatite crystallization. Dephosphorylation via a mechanism involving ALPL/TNAP promotes hydroxyapatite crystallization (By similarity). O-glycosylated. Isoform 5 is GalNAc O-glycosylated at Thr-59 or Ser-62. Belongs to the osteopontin family. Osteopontin entry