There is ample evidence from mouse and rat models of obesity and diabetes that β-cell mass increases to compensate for the additional insulin demand [13], [14] and that TMEM27 and BACE2 might play a role in regulating β-cell mass in ob/ob and db/db mice and in transgenic mouse models overexpressing TMEM27 or being BACE2 deficient [1], [2]. Here, CLTRN is linked to obesity due to melanocortin 4 receptor deficiency.