Endostatin is a 20 kDa proteolytic fragment of the C-terminal, non-collagenous (NC1) domain of type XVIII Collagen. It was originally identified as a factor produced by murine hemangioendothelioma cells that could specifically inhibit endothelial cell proliferation and angiogenesis. Although the molecular signals that trigger the release of Endostatin from type XVIII Collagen are not well understood, multiple proteases have been suggested to be involved in its generation including Cathepsins S, B, L, and V, Elastase, and matrix metalloproteinases (MMPs)-2, -7, and -9. Endostatin is of particular interest as it has been shown to inhibit the growth of many primary and metastatic tumors. It may also be involved in down-regulating angiogenesis during physiological processes such as wound healing and the establishment of placental circulation. The anti-angiogenic activity of Endostatin is attributable to its ability to inhibit endothelial cell proliferation and suppress VEGF-and FGF basic-induced endothelial cell migration and adhesion. Many of these effects are thought to be mediated by interactions between Endostatin and endothelial cell-expressed Transglutaminase 2, Heparin, and Integrins alpha 5 beta 1 and alpha V beta 3.