NOV (CCN3) is a member of the CCN family of secreted, cysteine-rich regulatory proteins that share four conserved modules which confer distinct biological activities. These modules include an insulin-like growth factor binding domain, a von Willebrand type C domain, thrombospondin-1 domain, and a C-terminal cysteine knot domain. NOV (CCN3) is 354 amino acid (aa) protein that shares an 80% aa identity with mouse, rat, and canine NOV (CCN3). It is widely expressed developmentally, especially in the muscle, endothelium, nervous system, adrenal cortex, and chondrocytes. NOV (CCN3) acts through the Notch and BMP signaling pathways to modulate self-renewal and maturation of a number of cell lineages including hematopoietic, osteogenic, and chondrogenic lineages. NOV (CCN3) is also a putative ligand for integrin receptors and is tightly associated with the extracellular matrix. Its interaction with integrins alpha v beta 3 and alpha 5 beta 1 mediates endothelial cell adhesion induces chemotaxis and promotes angiogenesis. The elevated expression of NOV (CCN3) is associated with certain tumors such as Wilm’s tumor and most nephroblastomas.