A new family of chloride transport proteins has recently emerged. These pro
teins have extensive homology to a protein previously isolated from bovine
tracheal epithelium that acts as a Ca2+-sensitive Cl- channel (CaCC) when h
eterologously expressed or when reconstituted into planar lipid bilayers. S
everal new members of this family have been identified in human, murine, an
d bovine epithelia, in addition to some other tissues, and are associated w
ith Ca2+-sensitive conductive chloride transport when heterologously expres
sed in Xenopus oocytes or HEK 293 cells. The expressed current is also sens
itive to inhibitors such as DIDS and niflumic acid. In addition, at least o
ne family member acts as an endothelial cell adhesion molecule. This emergi
ng family may underlie the Ca2+-mediated Cl- conductance responsible for re
scue of the cystic fibrosis (CF) knockout mouse from significant airway dis
ease.