We previously demonstrated in Drosophila that PLP deficiency caused by Pdxk or sgll/PNPO mutations, as well as by 4DP feeding, increased the hemolymph glucose content due to insulin resistance established with mechanisms not yet clarified (Marzio et al., 2014; Mascolo et al., 2020; Merigliano et al., 2018). Here, PNPO is linked to hyperinsulinemic hypoglycemia, familial, 4.