The RBC dehydration in sickle cell anemia is caused by facilitated K+ loss through hyperactivated KCNN4 (also known as the Gardos Channel in RBCs) and K+-Cl- cotransporter that is not compensated by uptake of equal amounts of Na+ (Clark et al., 1982; Izumo et al., 1987). Here, KCNN4 is linked to sickle cell disease.