These findings indicate that (a) exposure of normal HBE to SMM reproduces the up-regulation of IRE1α and XBP-1s found in inflamed, freshly isolated/native CF HBE (Figure 1; [28]) and (b) the increased expression of IRE1α and XBP-1s in CF HBE reflects an acquired response to the CF airway milieu. The gene discussed is ERN1; the disease is cystic fibrosis.