ACE2 is a type I integral membrane glycoprotein (15) expressed predominantly in the bronchus, lung parenchyma, heart, endothelium, kidneys, duodenum, and small intestine (16). ACE2 is a monocarboxypeptidase, unlike its homolog, ACE, which is a dipeptidase; ACE2 is not antagonized by ACE inhibitors (17). Although ACE contains 2 active catalytic domains, ACE2 has a single catalytic domain with 42% identical residues (18,19). The major substrate of ACE2 is Ang II, which upon C-terminus cleavage, produces angiotensin 1-7 (Ang1-7) and L-phenylalanine (20). Other substrates for ACE2 include Ang I, apelin-13, and dynorphin-13, which are catalyzed at much lower affinities (21). The non-catalytic C-terminal domain of ACE2 shares a 48% sequence homology with collectrin, a protein involved in neutral amino acid reabsorption from the intestine and the kidney (22,23). In the presence of a disintegrin and metalloproteinase 17 (ADAM17), also known as tumor necrosis factor (TNF)-α−converting enzyme (TACE), ACE2 exhibits ectodomain shedding (24), which results in the formation of a soluble enzyme. ACE2 also contains a calmodulin domain on its cytoplasmic tail that influences ectodomain shedding (25).