All of this provides strong evidence that the CUL3-KLHL3 E3 ligase complex regulates blood pressure via its ability to ubiquitinate WNK isoforms and that Gordon syndrome results in mutations that disrupt the formation of this complex’s ability to prevent WNK degradation and therefore stimulate renal salt retention by increased activation of NCC and NKCC2 by WNK isoforms in excess. This evidence concerns the gene SLC12A1 and Gordon syndrome.