CXCL4, also known as Platelet Factor 4, is a member of the CXC chemokine family, CXCL4. Human CXCL4 is a 101 amino acid (aa) protein with a 32 aa signal sequence and a 70 aa mature protein. CXCL4 has homology with IL-8 and beta-thromboglobulin. Human and mouse CXCL4 share a 64% identity. CXCL4 contains several heparin-binding sites at the C-terminal region. The active protein consists of a tetramer composed of individual CXCL4 subunits. Megakaryocytes synthesize CXCL4 and store it as tetramers in alpha-granules. The CXCL4 tetramers are secreted by activated platelets and can be measured at micromolar levels in serum. In contrast to other CXC chemokines, CXCL4 lacks chemotactic activity for polymorphonuclear granulocytes. CXCL4 does not contain an ELR motif. However, many other functions have been observed for CXCL4. CXCL4 is involved in monocyte survivial and differentiation into macrophages, and it has anti-angiogenic activity. CXCL4 has been demonstrated to inhibit the binding of FGF-2 to high-affinity receptors and its subsequent internalization. Cell surface neutrophil chondroitin sulfate chains serve as CXCL4 binding sites; affinity is controlled by the degree of sulfation of these chains.