Abstract This scientific commentary refers to ‘Inhibition of insulin-degrading enzyme in human neurons promotes amyloid-β deposition’ by Rowland et al. (https://doi.org/10.1042/NS20230016). Insulin-degrading enzyme (IDE) and neprilysin (NEP) have been proposed as two Aβ-degrading enzymes supported by human genetics and in vivo data. Rowland et al. provide complementary evidence of a key role for IDE in Aβ metabolism in human-induced pluripotent stem cell (iPSC)-derived cortical neurons.