The tight junction forms the paracellular permeability barrier in all epithelia, including the renal tubule. Claudins are a family of tight junction membrane proteins with four transmembrane domains that form the paracellular pore and barrier. Their first extracellular domain appears to be important for determining selectivity. A number of claudin isoforms have been found to be important in renal tubule function, both in adults and in neonates. Familial hypomagnesemic hypercalciuria with nephrocalcinosis is an autosomal recessive syndrome characterized by impaired reabsorption of Mg and Ca in the thick ascending limb of Henle's loop. Mutations in claudin-16 and 19 can both cause this syndrome, but the pathophysiological mechanism remains controversial.