Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Involved in the regulation of paracellular epithelia permeability to ions in multiple organs. It acts as a paracellular ion channel probably forming permselective pores; isoform 1 appears to create pores preferentially permeable to cations and isoform 2 for anions. In sweat glands and in the thick ascending limb (TAL) of Henle’s loop in kidney, it controls paracellular sodium permeability which is essential for proper sweat production and renal function (PubMed:19383724, PubMed:28771254, PubMed:28686597).
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