Pathways of the renin-angiotensin system (RAS) cascade. The classical RAS cascade is shown with light shading and includes the two major angiotensin II receptor subtypes, AT1 and AT2. Nonclassical components of the RAS cascade would include the ability of the (pro)renin receptor to activate prorenin, as well as enhance the activity of renin to metabolize angiotensinogen to Ang I, the ability of chymase to convert Ang I to Ang II, metabolism of Ang II to III and III to IV by aminopeptidases A and N, respectively, and the novel AT4 receptor for Ang IV which is also known as insulin-regulated aminopeptidase. In addition, there is the ACE2/Ang 1–7/mas axis of the RAS which is considered to be a counterregulator of the actions of the classical RAS. This includes the enzyme angiotensin-converting enzyme 2 (ACE2) which primarily forms Ang 1–7 from Ang II, but can also form Ang 1–9 from Ang I, prolylcarboxypeptidase which also forms Ang 1–7 from Ang II, and the enzymes neprilysin and prolylendopeptidase which forms Ang 1–7 directly from Ang I, and MAS, the putative receptor for Ang 1–7. The names of the genes that encode the various proteins of the RAS and related proteins are shown in italics after the protein names.