SLC12A3 and hypertensive disorder: 2011). SPAK knock‐in (KI) mouse model expresses a form of SPAK that cannot be activated by WNKs, resulting in a significant reduction in blood pressure (Rafiqi et al. 2010). Thus, WNK kinases modulate the activity of NCC in the DCT through a SPAK‐dependent mechanism. SPAK is therefore essential for the phosphorylation and activity of NCC, and this information, coupled with established links of several single nucleotide polymorphisms in the SPAK gene to hypertension, shows that SPAK has a key role in blood pressure regulation (Alessi et al. 2014).