Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermeable barriers, others mediate the permeability to ions and small molecules. Often, several claudin family members are coexpressed and interact with each other, and this determines the overall permeability. CLDN1 is required to prevent the paracellular diffusion of small molecules through tight junctions in the epidermis and is required for the normal barrier function of the skin. Required for normal water homeostasis and to prevent excessive water loss through the skin, probably via an indirect effect on the expression levels of other proteins, since CLDN1 itself seems to be dispensable for water barrier formation in keratinocyte tight junctions. Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN3, but not CLDN2, homopolymers. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with MPDZ and PATJ. Interacts with OCLN, CD81, CLDN4, CLDN6 and CLDN9 (By similarity). Associates with CD81 and the CLDN1-CD81 complex localizes to the basolateral cell membrane. Detected in epidermis and liver (at protein level). Widely expressed, with highest levels in liver and kidney. Complete perinatal lethality. Mice are born at the expected Mendelian rate, but die within one day after birth, due to severe defects in the skin barrier function, leading to rapid transepidermal water loss and dehydration. Belongs to the claudin family.