PAPP-A, which was first isolated in human pregnancy serum, belongs to the metzincin superfamily of metalloproteinases. PAPP-A circulates in pregnancy as a heterotetrameric disulfide-bound 2:2 complex composed of two 200 kDa PAPP-A subunits and two 50-90 kDa proform of eosinophil major basic protein (pro-MBP) subunits, denoted as PAPP-A/proMBP (~500kDa). Both PAPP-A and proMBP are synthesized in the placenta during pregnancy. Serum PAPP-A concentration increases exponentially throughout pregnancy until delivery and attains maximum levels at term. Heterotetrameric PAPP-A is highly efficient as a serum marker in first-trimester screening for Down’s syndrome (trisomy 21) and other fetal aneuploidies since low maternal serum levels have been associated with them. There is mounting evidence that low PAPP-A levels in the first trimester are also linked to adverse pregnancy outcomes such as preterm delivery, intrauterine growth retardation, preeclampsia, and stillbirth. Homodimeric PAPP-A also exists in serum, which circulates as a homodimer, not in complex with pro-MBP and associated with acute coronary syndrome (ACS) and other cardiac conditions.