Furthermore, previous studies found that PDIA1 contributes to oxidative maturation of proinsulin in the endoplasmic reticulum to support insulin production and ß-cell health in diet-induced obesity (Jang et al., 2019), indicating that P4HB could indirectly influence insulin production and ß-cell health. Here, P4HB is linked to obesity due to melanocortin 4 receptor deficiency.