2, 23 a protein that regulates membrane fusion events and participates in neurotransmission. WNK kinases affect cell growth and apoptosis through several pathways. 24–26 WNK1 is expressed ubiquitously, and its expression in the cardiovascular system in particular27 may account for the lethality of WNK1 deletion in utero. 28 WNK3 is highly expressed in the brain and may play an important role in the regulation of volume and intracellular ClJ in-aminobutyric acid–producing neurons. 20, 29 Finally, WNK kinases modulate ion transport across epithelia (see below). Despite these diverse and essential functions, WNK kinase mutations identified in humans cause a phenotype that results predominantly from kidney dysfunction, although minor effects in other organ systems may be present. 30 Diseasecausing WNK1 mutations are large deletions in the first intron that do not change the coding sequence. 10 These intronic mutations are believed to increase WNK1 protein expression, 10 although this observation has not been corroborated in renal tissue. FHHt-causing WNK4 mutations are missense mutations located within 2 discrete regions (see Figure 1), the first within an acidic motif adjacent to the first coiled coil domain and the second adjacent to the second coiled coil domain. 10, 31 The FHHt-causing WNK4 mutations lie outside the kinase domain.