However, upon higher levels of ER stress as observed in obesity, a “pathophysiological” ER stress shifts the UPR to a terminal signaling cascade that induces apoptosis, notably via C/EBP homologous protein (CHOP), an apoptotic transcription factor whose expression is highly induced by ER stress in β-cells [6]. The gene discussed is DDIT3; the disease is obesity due to melanocortin 4 receptor deficiency.