Transmembrane protein which can modulate activity of various signaling pathways, probably via binding to integrin ITGAV:ITGB3 (PubMed:18366072, PubMed:22492581, PubMed:29702220). Mediates heterophilic cell-cell interactions in vitro (PubMed:18366072). Inhibits osteoclastogenesis downstream of TNFSF11/RANKL and CSF1, where it may function by attenuating signaling via integrin ITGB3 and MAP kinase p38 (PubMed:22492581). Plays a role in cartilage formation where it promotes proliferation and maturation of growth plate chondrocytes (PubMed:29702220). Stimulates formation of primary cilia in chondrocytes (PubMed:29702220). Enhances expression of genes involved in the hedgehog signaling pathway in chondrocytes, including the hedgehog signaling molecule IHH; may also promote signaling via the PTHLH/PTHrP pathway (PubMed:29702220). Plays a role in angiogenesis where it suppresses migration of endothelial cells and also promotes their apoptosis (By similarity). Inhibits VEGF-induced activation of AKT and p38 MAP kinase in endothelial cells (By similarity). Also inhibits VTN (vitronectin)-mediated integrin ITGAV:ITGB3 signaling and activation of PTK2/FAK (By similarity). May play a role in the maturation and maintenance of the blood-brain barrier (PubMed:14603461). Homodimer in cis (PubMed:18366072). Does not appear to form trans-homodimers (PubMed:18366072). Interacts with ITGB3; the interaction inhibits ITGAV:ITGB3 heterodimer formation (PubMed:22492581). Primarily localizes to the cell membrane (PubMed:18366072). Detected in the cilium of primary chondrocytes (PubMed:29702220). Highly expressed at areas of cell-cell contact and may localize to tight junctions (PubMed:18366072). Also found in the nucleus where it is detected in the soluble (as opposed to chromatin-bound) fraction (PubMed:18366072). Widely expressed (at protein level) (PubMed:18366072). Highly expressed in brain where it localizes to the glia limitans, which is formed by the endfeet of astrocytes surrounding capillaries, and beneath the pia mater (at protein level) (PubMed:14603461). In lung, detected in epithelial cells of the bronchus (at protein level). Expressed in intercalated disks in the heart (at protein level) (PubMed:18366072). Detected in pancreatic alpha-cells in the islet of Langerhans (at protein level) (PubMed:18366072). In kidney, found in the brush border of the proximal convoluted tubule (at protein level) (PubMed:18366072). Expressed in the epithelium of the small intestine (at protein level) (PubMed:18366072). Weakly expressed in liver (at protein level) (PubMed:18366072). Detected in myeloid cells (PubMed:22492581). At embryonic stage 15.5 dpc, expressed in the growth plate of long bones where it is mostly found in chondrocytes in the resting and proliferative zones (at protein level) (PubMed:29702220). Expression gradually increases in differentiating osteoclasts, but then decreases during the late stages of differentiation (PubMed:22492581). Disruption of the blood-brain barrier by cold injury results in a drastic reduction in expression (PubMed:14603461). Up-regulated in primary chondrocytes in response to BMP2 and PTHLH/PTHrP (PubMed:29702220). RGD motif 2 (but not RGD motif 1) is involved in integrin ITGAV:ITGB3 binding.