The archetypal example of this is type II pseudohypoaldosteronism (Gordon’s syndrome), in which inherited mutations in the Wnk-SPAK kinase cascade or the KLHL3–CUL3 ubiquitin ligase complex that regulates it lead to the constitutive phosphorylation (and therefore activation) of NCC [30]. This evidence concerns the gene SLC12A3 and pseudohypoaldosteronism type 2.