Claudins are a family of proteins that are the most important components of the tight junctions, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an epithelium. They have similar structures with four transmembrane domains, with the N-terminus and the C-terminus in the cytoplasm. Claudin-16 is primarily found in the kidneys and is responsible for regulating the reabsorption of magnesium and calcium ions. Mutations in the Claudin-16 gene can lead to a rare genetic disorder called familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC).