Claudins family member Claudin18 (CLDN18) is a four-pass transmembrane protein with two extracellular loops and cytoplasmic N- and C-tails found in tight junctions. CLDN18 modulates paracellular permeability, polarity, and signaling. CLDN18 deficiency has been associated with atrophic gastritis, spasmolytic polypeptide-expressing metaplasia (SPEM), and asthma. Lung-specific CLDN18.1 modulates alveolar epithelial type II (AT2) cell proliferation and organ size. Restoration of CLDN18.1 expression in human lung cancer cells has been shown to suppress proliferation, inhibiting the IGF-1R/AKT axes. Not expressed in other healthy tissues, gastric mucosa-specific isoform CLDN18.2 expression manifests in primary gastric cancers. CLDN18.2 at the surface of epithelial tumor cells is a target in antibody and CAR-therapies currently in development.