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Claudin-6 (CLDN6) is a member of the claudin family and serves as a tight junction molecule, which plays a vital role in cell-to-cell adhesion in epithelial or endothelial cell sheets. CLDN6 has been identified to be the origination of cell adhesion signaling taking part in the regulation of nuclear receptor activity through targeting molecules of the nuclear receptor superfamily and managing their gene expression. In terms of its various characters in human cancers, CLDN6 may be a helpful positive marker for further identification of atypical teratoid/rhabdoid tumors (AT/RTs) for diagnosis and therapy. CLDN6 is also reported to be a possible single prognostic marker and promising therapeutic target for a subgroup of intestinal type gastric cancer.