Previous studies reported that IRE1α was involved in the activation of autophagy,[9] and that SEL1L‐HRD1 ERAD regulated IRE1α activation through promoting its degradation.[44] This study further suggests an improved understanding on the cell type‐specific function of ERQC pathways in orchestrating the ER proteostasis on endocrine neurons, as well as their interplay in the pathogenesis of various protein‐misfolding related human diseases, such as endocrine neuron dysfunction, neurodegenerative diseases, and diabetes. This evidence concerns the gene ERN1 and diabetes mellitus.