Insulin-Degrading Enzyme (IDE) is a secreted enzyme that belongs to the peptidase M16 family. IDE is a large zinc-binding protease and cleaves multiple short polypeptides that vary considerably in sequence. IDE plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin, and other peptides, and thereby plays a role in intercellular peptide signaling. IDE degrades amyloid formed by APP and IAPP. IDE may participate in the degradation and clearance of naturally secreted amyloid β-protein by neurons and microglia. IDE, which migrates at 110 kDa during gel electrophoresis under denaturing conditions, has since been shown to have additional substrates, including the signaling peptides glucagon, TGF α and β-endorphin.