The claudin superfamily consists of many structurally related proteins that are important structural and functional components of tight junctions. Claudin-12, also known as CLDN12, is a 244 amino acid multi-pass membrane protein that is expressed in the brain, duodenum, jejunum, ileum, and colon. Claudin-12 localizes to cell junctions and may be involved in tight junction integrity by regulating hyperammonemia. Ammonia can alter brain capillary endothelial cell gene expression and transporter function. Claudin-12 is upregulated in enterocytes through vitamin D receptors which strongly suggest that claudin-12 forms paracellular Ca(2+) channels in intestinal epithelia and may be critical for vitamin D-dependent calcium homeostasis.