IRE1α is one of the key UPR transducers in the pathogenesis of obesity-related inflammation by activating cytokine transcription factor AP-1 through JNK and by increasing the NF-κB nuclear translocation through promoting degradation of IκB by IKK-mediated phosphorylation [226,227]. The gene discussed is MAPK8; the disease is obesity due to melanocortin 4 receptor deficiency.