Several mutant hemoglobins (Hbs) can protect against the life-threatening effects of Plasmodium falciparum malaria. For example, HbC – in which substitution of lysine for glutamate at position 6 of the β-chain accelerates the oxidation of Hb to insoluble hemichromes – reduces the risk of developing severe malaria in homozygous individuals. On p. 1091, James Dvorak and colleagues report that this protection may result from HbC's effects on the clustering of host erythrocyte membrane band 3. This protein normally exists as dimers in erythrocyte membranes but forms larger clusters when hemichrome is deposited below the membrane during erythrocyte senescence or a P. falciparum infection. Autoantibody recognition of these clusters targets the erythrocyte for destruction. When the authors used a quantum dot technique to determine the surface distribution of band 3 molecules on P. falciparum-infected erythrocytes, they found more and larger clusters on HbC homozygous erythrocytes than on normal erythrocytes. They conclude that increased band 3 clustering may enhance autoantibody recognition sites and thereby help HbC to protect against malaria.