Aberrantly upregulated BACE1 degradation of functional membrane IR in the liver and increased plasma soluble IR are observed in diabetic patients (Bao et al., 2021) as well as in db/db (Meakin et al., 2018a) and HFD (Lin et al., 2025) mouse models of type 2 DM, representing a mechanism of directly BACE1-mediated insulin resistance. The gene discussed is BACE1; the disease is Insulin resistance.