Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN3, but not CLDN1, homopolymers. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Expressed in the kidney, liver and intestine, with higher levels in the ileum than in the jejunum. Low levels in the brain. By CDX1 and CDX2. Induction by CDX2, but not CDX1, is potentiated by TCF1. The disulfide bond is necessary for pore formation, but is not required for correct protein trafficking. Both female and male Cldn2-knockout mice are similarly hypercalciuric compared to wild-type littermates. Cldn2-null mice are hypercalciuric due to a primary defect in renal tubule calcium transport and develop papillary nephrocalcinosis. Cldn2-null mice are also found to have increased net intestinal calcium absorption, but reduced paracellular calcium permeability in the colon, suggesting reduced intestinal calcium secretion. Belongs to the claudin family.