Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium- independent cell-adhesion activity. May form permselective paracellular pores, isoform 1 appears to create pores preferentially permeable to cations and isoform 2 for anions. Plays a key role in controlling cation selectivity and transport in the thick ascending limb (TAL) of Henles loop in kidney.