Tight junctions mediate the regulation of the paracellular pathway between epithelial and endothelial cells. They form close connections to eliminate the extracellular space and regulate the flow of solutes between cells. The human gene PCLN-1 (paracellin-1) is related to the claudin family of integral membrane proteins, which localize to tight junctions. PCLN-1 contains four transmembrane domains and intracellular amino and carboxy termini, characteristic of the other claudin family members, and is detected only at the tight junctions of kidney tissue. PCLN-1 forms an intercellular pore and controls the resorption of magnesium and calcium in the thick ascending limb of Henle (TAL). Mutations in PCLN-1 cause renal magnesium wasting, which may contribute to a rare autosomal recessive disease, renal hypomagnesemia with hypercalciuria and nephrocalcinosis.