ACE has long been recognized as the key enzyme within the renin-angiotensin system (RAS) mainly by cleaving angiotensin (Ang) I to form Ang II, which is the main active peptide within the system. ACE2, a homologue of ACE, is a monocarboxypeptidase that preferentially removes carboxy-terminal amino acids from various substrates, including Ang II, Ang I, and apelin. ACE2 cleaves Ang II to form Ang-(1-7) with a high catalytic efficiency, suggesting an important role in preventing Ang II accumulation, while enhancing Ang-(1-7) formation (Fig. 1). Other mammalian homologues of ACE, such as collectrin and, more recently, ACE3, have also been described. ACE2, however, is the only known homologue of ACE with enzymatic activity.