Using mouse genetics we provide evidence that VPS13C plays a role in the control of pancreatic β-cell function. It should be emphasized that the impact of deleting this gene selectively in the β-cell was relatively mild and indeed was not apparent in males until 20 wk of age. Evidence for deficiencies in β-cell function were, however, more apparent in females from an earlier age, in line with the human eQTL data. These included the transient appearance of glucose intolerance at 12 wk and its reemergence at 20 wk. Interestingly, the same phenomenon is also observed in a monogenic form of diabetes resulting from misexpression of the ZAC gene, termed transient neonatal diabetes mellitus (TNDM), and is apparent in mouse models with this disease (albeit in younger animals than observed here) (38). While the reasons for this transience are not known either in TNDM or in the case of Vps13c deletion, dynamic changes in the balance between islet function and insulin sensitivity may provide one explanation. Similarly, the emergence of glucose intolerance with age in βVps13cKO mice, which is reminiscent of changes seen after the inactivation of the T2D GWAS gene Tcf7l2 in mice (43, 82), seems to reflect, at least in part, increasing insulin resistance as well as impaired insulin output from the pancreas. Of note, recent studies report relatively preserved glucose sensing of isolated islets with age in both mice and humans (3, 26) but suggest a role for altered vascularization and fibrosis in impaired insulin secretion in vivo (3).