The Na/HCO3 cotransporter NBCn1 (SLC4A7) plays critically important roles in physiology and pathology.In human, genetic studies have shown that SLC4A7 are associated with hypertension and breast cancer.In mice, genetic disruption in Slc4a7 causes blindness and deafness, a phenotype commonly observed in Usher syndrome.The mechanism underlying the functional regulation ofNBCn 1 largely remains unknown.In the present study, we investigated the protein interaction ofNBCnl carboxyl terminus (Ct).By yeast two hybrid, we identified activin receptor-interacting protein 2 (ARIP2), a scaffolding PDZ protein that has strong interaction with NBCn1 Ct.Removal of the PDZ-binding motif"ETSL" abolishes, whereas deletion of the alternative cassette Ⅲ of NBCnl Ct has no effect on its interaction with ARIP2.ARIP2 is reported to be involved in the regulation of membrane receptors by endocytosis.We hypothesize thatARIP2 play important roles in the functional regulation ofNBCn1.