Endostatin is a C-terminal proteolytic fragment of collagen XVIII α1 (Col 18) that is localized in the vascular basement membrane of almost all epithelia and endothelia. Endostatin is produced from catalytic cleavage from MMPs, cathepsin L, and S. It is detected in circulation at a physiologic level of 20 to 50 ng/ml in serum. Crystal X-ray analysis of endostatin has shown a compact globular structure, with one face rich in arginine residues that acts as a heparin-binding motif. Endostatin interacts with multiple molecules including heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, thrombospondin-1, SPARC, collagens (I, IV, and VI), the amyloid peptide Aβ (1-42), transglutaminase-2, and among others. Endostatins derived from collagens XV and XVIII differ in structure and binding properties, tissue distribution, and anti-angiogenic activity. Endostatin is an endogenous angiostatic factor that induces apoptosis in endothelial cells and inhibits endothelial cell migration in vitro. Col 18-null mice showed faster tumor growth when implanted with tumor cells that do not produce Col 18. Overexpression of circulating endostatin in transgenic mice resulted in reduced tumor growth. Experimental model of glomerulonephritis in Col 18-null mice showed that the absence of this molecule exacerbates immune-mediated glomerulonephritis.