Claudin-8 is a tight junction protein expressed in several mouse distal nephron segments, suggesting that it may contribute to the paracellular barrier that protects transtubular Na+, K+, and H+ gradients in the distal nephron. Caludin-8 decreases paracellular permeability to cations when overexpressed in MDCK-II cells, suggesting that it may function as a paracellular cation barrier. Caludin-8 is also found in the thin ascending limb of Henle, a segment of the nephron that is known to be leaky to Na+. Claudin-8 is expressed primarily in tight junctions along the entire aldosterone-sensitive distal nephron (ASDN) and in the late thin descending limb of Henle, consistent with its role as a paracellular cation barrier protein. Claudin-8 is found in umbrella cell tight junctions in the bladder epithelium. Expression of Claudin-8 has also been reported in the inner ear.