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Claudin-2 is a tight junction membrane protein that can create a pathway selective for small positively charged ions between epithelial cells. Its presence can make a junction more conductive without creating an indiscriminate hole through the epithelial sheet.

Researchers expressed claudin-2 in an epithelial layer that initially had low conductance between cells. Conductivity increased, and comparison of different salts showed preferential passage of cations over anions.^[ref] This is a useful counterexample to treating every claudin as a simple seal: changing the molecular composition of a tight junction can change both how much passes and which substances pass.

Mikio Furuse investigated the molecular construction of tight junctions. In a 1998 study, introducing claudin-1 or claudin-2 into fibroblasts that normally lack tight junctions produced networks of junction-like strands at contacts between cells. Immunofluorescence located the introduced proteins, while freeze-fracture imaging revealed the strand architecture.^[ref]

The experiment demonstrated that either claudin could build a key structural feature in a simplified cellular setting. Recruitment of occludin further distinguished a strand-forming component from another associated junctional protein.

Salah Amasheh studies the selective barrier formed by epithelium. A 2002 study led by Amasheh tested whether claudin-2, a tight junction protein, could change the passage of ions between neighboring biological cells. The investigators introduced Complementary DNA encoding claudin-2 into a normally resistant cultured kidney epithelium, checked where the protein appeared, and compared electrical measurements with control cultures.^[ref]

Claudin-2 expression increased conductivity through the spaces between biological cells by a factor of 5.6 and favored cations over anions. Transport of several larger test substances did not increase. The result illustrates a selective channel rather than an indiscriminate hole: greater passage of one class of ions need not mean greater passage of every dissolved substance. Combining localization, controls and measurements of different solutes made the interpretation stronger than an electrical measurement alone.^[ref]