This study presents findings from a mouse model of airway mucus dehydration and obstruction elicited by overexpression of an epithelial ion channel, βENaC, which support a hypothesis that NLRP3 inflammasome activation and dysregulated S1P signalling are associated with mucus obstruction, the common pathologic component in CF, COPD and other muco-obstructive diseases (summarized in Fig. 9). This evidence concerns the gene MBTPS1 and cystic fibrosis.