Plays a role in the cellular breakdown of insulin, APP peptides, IAPP peptides, natriuretic peptides, glucagon, bradykinin, kallidin, and other peptides, and thereby plays a role in intercellular peptide signaling (PubMed:10684867, PubMed:17051221, PubMed:17613531, PubMed:18986166, PubMed:19321446, PubMed:21098034, PubMed:2293021, PubMed:23922390, PubMed:24847884, PubMed:26394692, PubMed:26968463, PubMed:29596046). Substrate binding induces important conformation changes, making it possible to bind and degrade larger substrates, such as insulin (PubMed:23922390, PubMed:26394692, PubMed:29596046). Contributes to the regulation of peptide hormone signaling cascades and regulation of blood glucose homeostasis via its role in the degradation of insulin, glucagon and IAPP (By similarity). Plays a role in the degradation and clearance of APP-derived amyloidogenic peptides that are secreted by neurons and microglia (Probable) (PubMed:26394692, PubMed:9830016). Degrades the natriuretic peptides ANP, BNP and CNP, inactivating their ability to raise intracellular cGMP (PubMed:21098034). Also degrades an aberrant frameshifted 40-residue form of NPPA (fsNPPA) which is associated with familial atrial fibrillation in heterozygous patients (PubMed:21098034). Involved in antigen processing. Produces both the N terminus and the C terminus of MAGEA3-derived antigenic peptide (EVDPIGHLY) that is presented to cytotoxic T lymphocytes by MHC class I. {ECO:0000250|UniProtKB:Q9JHR7, ECO:0000269|PubMed:10684867, ECO:0000269|PubMed:17051221, ECO:0000269|PubMed:17613531, ECO:0000269|PubMed:18986166, ECO:0000269|PubMed:19321446, ECO:0000269|PubMed:20364150, ECO:0000269|PubMed:21098034, ECO:0000269|PubMed:2293021, ECO:0000269|PubMed:23922390, ECO:0000269|PubMed:24847884, ECO:0000269|PubMed:26394692, ECO:0000269|PubMed:26968463, ECO:0000269|PubMed:29596046, ECO:0000269|PubMed:9830016, ECO:0000305|PubMed:23922390}. (Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV). . This is the function of IDE (insulin degrading enzyme, Ensembl gene identifier ENSG00000119912).