Claudin-18 is a tight junction protein expressed as lung-and stomach-specific isoforms which are generated by alternative splicing of the claudin-18 gene. The lung-specific form is a downstream target gene regulated by the T/EBP/NKX2.1 transcription factor. A splice variant lacking the C-terminal cytoplasmic domain also exists in mouse, but has not been confirmed in human. Human claudin-18 demonstrates 88% amino acid sequence identity to the mouse protein. Immunohistochemical studies have demonstrated complete membrane localization of claudin-18 in lung and stomach epithelial cells, while electron microscopy has shown that it is concentrated in the cell-cell borders of these cells. These features suggest a potentially important role for claudin-18 in the structure and function of tight junctions in the lung and stomach. Claudin-18 expression has also been reported in the inner ear.