Biophysical studies using X-ray crystallography [2,4,5] and cryogenic electron microscopy [6] have revealed mechanisms by which IDE encloses and degrades a diverse group of metabolically important and pathologically relevant substrates including insulin, a key hormone for glucose metabolism, amyloid-β(1-42) (Aβ42), which self-assembles to form the proximate neurotoxic assemblies in Alzheimer’s disease (AD) [7], and islet amyloid polypeptide (IAPP), which self-assembles to form pancreatic amyloid in type 2 diabetes (T2D) [8]. This evidence concerns the gene INS and early-onset autosomal dominant Alzheimer disease.