IDE (insulin-degrading enzyme) is a highly conserved zinc metalloprotease that primarily functions to degrade insulin and other intermediate-size peptides 1. The enzyme plays a crucial role in hepatic insulin clearance, a physiological process that clears approximately 50-80% of circulating insulin in response to nutritional cues 1. IDE exhibits endopeptidase activity and requires zinc ion binding for its catalytic function, as indicated by GO annotations. Beyond insulin metabolism, IDE is involved in amyloid-beta clearance and metabolic processes, suggesting broader roles in protein homeostasis. In disease contexts, IDE shows altered expression patterns in Alzheimer's disease, with decreased expression observed in brain samples from AD patients compared to healthy controls 2. Additionally, genetic polymorphisms in IDE, particularly rs1887922, are associated with increased risk of Alzheimer's disease 3. Both insulin clearance and IDE activity are reduced in diabetic patients, though the cause-effect relationship remains unproven in humans 1. This has led to interest in developing IDE inhibitors as potential therapeutic approaches for diabetes treatment, though the clinical significance of this strategy requires further investigation 1.