BPIFA1 and cystic fibrosis: The low-volume hypothesis of CF lung disease links increased activity of ENaC with ASL depletion in CF3 and so reducing transepithelial sodium absorption through ENaC is an alternative target for therapeutics.11 36 The role of ENaC in regulating ASL volume has been validated in recent work showing that inhibition of ENaC proteolytic activation using the SPLUNC1 or peptide fragments37–39 or QUB-TL140 successfully prevented dehydration of the ASL in CF HBEC monolayers.