Peer-review started: September 8, 2015
First decision: September 29, 2015
Revised: October 19, 2015
Accepted: December 9, 2015
Article in press: December 11, 2015
Published online: January 6, 2016
Processing time: 123 Days and 22.7 Hours
Core tip: NFAT5 is critical for kidney functions. Its dis-regulation results in or is associated with the renal diseases and disorders. More than a dozen of kinases have been identified to contribute to tonicity-dependent regulation of NFAT5. The present review is focused on how these kinases regulate NFAT5 activity under the context of hypertonicity or hypotonicity. Understanding these regulatory mechanisms will have therapeutic implications. A precedent example is that recognition of the cyclosporine immunosuppressive effect resulted from inhibition of the phosphatase calcineurin-dependent activation of NFAT1 allows combination use of cyclosporine with other mechanistically different immunosuppressants to improve their therapeutic efficacy and reduce their side effects.