IDE (Insulin-degrading enzye, INSULYSIN) is a zinc metallopeptidase that functions in intracellular signaling by degrading and terminating the activity of a number of peptides including insulin, glucagon, amylin, kallidin, and bradykinin. IDE is involved in regulating the insulin-mediated inhibition of amyloid-beta peptide degradation. A decrease in IDE expression results in a loss in amyloid-beta degradation (and a consequential increase in cerebral accumulations of amyloid-beta) and may contribute to the pathogenesis of Alzheimer’s disease. IDE dysfunction is correlated with Alzheimer's disease and also with type 2 diabetes mellitus, but IDE mutations have not been clearly demonstrated to cause either. In immunohistochemistry, IDE has primarily cytoplasmic positivity with some extracellular or membranous localization, and it is found in all tissues throughout the body. References: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4162-7, PMID: 12634421; Alzheimers Dement (Amst). 2019 Dec; 11: 392–404, PMID: 31193223; Journal of Biomedicine & Biotechnology. 2006 (3): 58406, PMID: 17047308.