When dietary potassium deficiency occurs, the concentration of extracellular K+ decreases, and Kir4.1/5.1 hyperpolarizes the cell membrane and causes NCC activation through the WNK-SPAK-NCC pathway to limit potassium loss, sometimes even at the cost of increasing blood pressure (Terker et al., 2015; Welling, 2016). Here, SLC12A3 is linked to potassium deficiency.