Although the relevance of XBP-1 signaling resulting from exaggerated ER expression of ΔF508 CFTR in cell lines needs to be properly evaluated, the data from primary cultures of inflamed CF airway epithelia expressing endogenous ΔF508 CFTR levels indicate that the CF airway environment, rather than the mutant CFTR, is responsible for promoting ER stress coupled to increased levels of XBP-1s. Here, XBP1 is linked to cystic fibrosis.