HCO₃^– is taken up from the serosal space and transported into the gut lumen in a CFTR-dependent manner by the enterocyte. CFTR acts as an HCO₃^– channel to directly transport HCO₃^– and also acts indirectly by supplying Cl^– to the lumen, which is then exchanged for HCO₃^– (arrow) by Cl^–/HCO₃^– exchangers. The study in this issue by Garcia et al. (6) reports that HCO₃^– and CFTR are required for mucin secretion. The authors propose that, upon mucin secretion from goblets cells into the lumen, the mucins (previously condensed into mucin granules) rapidly disassociate from Ca²⁺ and H⁺ ions, which allows mucin expansion and disaggregation and the formation of a normal mucus layer. However, Garcia et al. also report that direct addition of HCO₃^– to the gut lumen is insufficient to support mucin release. This suggests the possibility that HCO₃^– does not act at the luminal surface in mucin release. Are there intracellular functions of HCO₃^– and CFTR, such as fostering intercellular communication between the enterocyte and the goblet cell (e.g., intracellular pH regulation and gap junction communication), that potentiate mucin granule exocytosis?