The tight junction (TJ) system is primarily responsible for establishing the paracellular barrier function of epithelial cell sheets. The TJ is a supramolecular complex containing transmembrane proteins associated with membrane-scaffolding proteins such as ZO-1/2 and cingulin that allows the dynamic regulation of ion and solute passage across the paracellular space. Among the TJ transmembrane proteins, claudins are specifically required to form the TJ strands that organize the paracellular barrier structure. The multi-gene claudin family has at least 27 members in human and mouse. Although claudins are paracellular barrier-forming proteins, certain “ion leaky” claudins specify which ions can cross the barrier. A remarkable characteristic of claudin family proteins is their distinct tissue-dependent expression patterns. In our laboratory, some claudins such as claudins 2,15,18 have recently been intensively studied with regard to their biological roles in processes such as inflammation and nutrient absorption. These studies highlight the functions of claudin beyond that of a simple barrier.