This activity was observed over sixty years ago,[10] though the enzyme specifically responsible for B chain cleavage was identified more recently.

[11] This discovery revealed considerable amino acid sequence similarity between IDE and the previously characterized bacterial protease pitrilysin, suggesting a common proteolytic mechanism.

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 alpha, and β-endorphin.

Aβ is a byproduct generated as the result of proteolytic processing of the amyloid precursor protein (APP) by proteases referred to as the β and γ secretases.

[15] Studies of genetically inherited forms of Alzheimer's show reduction in both IDE expression[16] and catalytic activity[17] among affected individuals.

These may be diverse, as IDE has been localized to several locations, including the cytosol, peroxisomes, endosomes, proteasome complexes,[18] and the surface of cerebrovascular endothelial cells.

[24] Recent studies have observed that the oligomerization of synthetic Aβ was completely inhibited by the competitive IDE substrate, insulin.

The first step of one proposed mechanism[25] includes a zinc-bound hydroxide group performing a nucleophilic attack on a carbon substrate that materializes into the intermediate INT1.

In this species, we can note that the zinc-bound hydroxide is completely transferred on the carbonyl carbon of substrate as a consequence of the Zn2+−OH bond breaking.