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Protein family review The claudins Madhu Lal­Nag* and Patrice J Morin*† Addresses: *Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, National Institutes of Health Biomedical Research Center, MD 21224, USA. †Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA. Correspondence: Patrice J Morin. Email: morinp@ development [2]. Consistent with this hypothesis is the Summary presence of highly homologous CLDN genes located in The claudin multigene family encodes tetraspan membrane proteins that are crucial structural and functional components of close proximity in various mammalian genomes (see tight junctions, which have important roles in regulating para­ below). Interestingly, the genome of the puffer fish cellular permeability and maintaining cell polarity in epithelial Takifugu has a large number of claudin genes (at least 56) and endothelial cell sheets. In mammals, the claudin family as the result of extensive gene duplication [3]. Claudin­ consists of 24 members, which exhibit complex tissue­specific like genes have been reported in lower chordates (the patterns of expression. The extracellular loops of claudins from ascidian Halocynthia roretzi), as well as in invertebrates adjacent cells interact with each other to seal the cellular sheet and regulate paracellular transport between the luminal and (Drosophila) [4], but the exact roles of these claudins in basolateral spaces. The claudins interact with multiple proteins