Because the essential salt-transporters NKCC2 and NCC require cAMP for proper expression and functioning our finding of Gαs mistargeting and impaired cAMP generation in MAGED2-depleted hypoxic cells may explain, at least in part, the transient nature of antenatal Bartter syndrome caused by MAGED2 mutations and reveal potential strategies of intervention in this disease and beyond. Here, MAGED2 is linked to Bartter syndrome.