However, we bring the evidence that MSI-1436 application may represent an efficient genetic inhibitor of certain aspects of IRE1α activity for the attenuation of sustained XBP1 expression and unconventional splicing under unfavourable metabolic conditions in the liver, as previously reported by Bailly-Maitre and colleagues (79), who uncovered that the inhibition of IRE1α-mediated XBP1 splicing using Bax-inhibitor 1 protects mice from obesity-associated insulin resistance development. The gene discussed is ERN1; the disease is obesity due to melanocortin 4 receptor deficiency.