Mutated Gardos channel is activated by 10 times lower Ca²⁺ concentration and shows abnormally slow inactivation kinetics. These combined effects lead to excessive loss of K⁺ (A) and red blood cell dehydration (B), which is associated with hemolytic anemia. The disease causing the Arg352His mutation (red dot) is located in the highly conserved region of the calmodulin binding domain of the Gardos channel; calmodulin with bound Ca²⁺ ions is shown in pink. The other disease-causing mutations identified as Val282Met and Val282Glu are located in the predicted transmembrane loop S6 of the channel. Professional illustration by Patrick Lane, ScEYEnce Studios.