Puzzle resolved: CFTR mediates chloride homeostasis by segregating absorption and secretion to different cell types.

In the lungs, the cystic fibrosis transmembrane conductance regulator (CFTR) regulates ion transport in surface-airway epithelia and submucosal glands, thus determining airway surface liquid (ASL) volume and mucus hydration. In this issue of the JCI, Lei Lei and colleagues report that the CFTR-rich and barttin/Cl- channel-expressing ionocytes mediate chloride absorption across airway epithelia, whereas the more abundant basal cells and secretory cells mediate chloride secretion. Thus, CFTR-mediated secretion and absorption of chloride ions in the lung are segregated by cell type, which has implications for future molecular therapies for cystic fibrosis lung disease.