Pappalysin-1/PAPP-A: ProductsPappalysins comprise one of the five families of Metzincins (other families include ADAMs/ADAMTSs, MMPs, Astacins, and Serralysins). Pappalysin-1 (PAPP-A) is an important pregnancy protein and increases in plasma by a factor of about 150 during pregnancy. Reduced maternal serum PAPP-A is a major marker of Down syndrome in the first trimester of pregnancy. PAPP-A cleaves IGFBP-4 and -5 (insulin-like growth factor-binding protein-4 and 5) at a single site, resulting in the release of bioactive IGF. Pappalysin-2 (PAPP-A2; also called PAPP-E) shares 45% amino acid identity with PAPP-A and cleaves IGFBP-2.