Figure 1. Major salt reabsorption pathways modulated by SPAK in the kidney.

The nephron is the functional unit of the kidney (left lower corner). NKCC2 and NCC are key proteins involved in transport pathways driving salt reabsorption in the apical membrane of the thick ascending limb of Henle's loop (TAL; in red) or distal convoluted tubule (DCT; in blue). Rafiqi et al demonstrate that SPAK is expressed in these segments of the nephron and that absence of SPAK activity is associated with reduced NKCC2 and NCC expression and activity resulting in reduction of arterial blood pressure. These observations support the hypothesis that WNKs effect on NKCC2 or NCC is mediated by SPAK.