Thrombopoietin (TPO), is a key regulator of megakaryocytopoiesis and thrombopoiesis in vitroand in vivo. TPO has been purified and cloned from several species including mouse, rat, and dog. The proteins from the various species are highly conserved, exhibiting from 69-75% sequence identity at the amino acid sequence level. Mature TPO can be divided into two domains: the amino-terminal half with homology to erythropoietin (Epo) and the carboxy-terminal half rich in serine, threonine and proline residues and containing seven potential N-linked glycosylation sites. The carboxy terminus domain of TPO has been shown to regulate the specific activity and circulating half-life of TPO. The carboxy-terminal may also have a role in promoting the efficient biosynthesis and secretion of TPO.