Pregnancy-associated plasma protein-A (Pappalysin-1 or PAPP-A), also known as Insulin-like growth factor-dependent IGF-binding protein 4 (IGFBP4) protease, is a member of the peptidase M43B family of proteins. PAPP-A, a metalloproteinase, cleaves Insulin-like growth factor binding proteins IGFBP4 and IGFBP5, releasing bound IGF. PAPP-A is primarily expressed in septa and anchoring villi in placenta and is also expressed in pregnancy serum. Levels of PAPP-A increase throughout pregnancy. Lower levels of expression can be detected in kidney, prostate, breast, ovary and endometrial tissues. PAPP-A is a secreted protein that can form homodimers; in pregnancy serum PAPP-A may also form a heterotetramer with PRG-2.