Insulin-degrading enzyme, also known alternatively as IDE, insulysin or insulin protease, is a large zinc-binding protease of the M16 metalloprotease family known to be responsible for insulin degradation. In addition to insulin, IDE degrades many targets including glucagon, atrial natriuretic peptide, and beta-amyloid peptide, regulates proteasomal degradation and other cell functions. IDE represents a pathophysiological link between type 2 diabetes (T2DM) and late onset Alzheimer's disease (AD). Potent and selective modulators of IDE activity are potential drugs for therapies of both diseases.