(A) In normal cells, the α-globin locus on chromosome 16 and β-globin locus on chromosome 11 produce α- and β-globin mRNA and α- and β-globin polypeptides, respectively, which combine with the heme moiety to form Hb dimers (Hbαβ). Two Hbαβ dimers combine and form the Hb tetramer HbA. AHSP stabilizes and solubilizes newly formed and excess α-globin chains as apo-α-globin and αHb. The absence of AHSP normally leads to a mild anemia due to precipitated unstabilized α chains (not shown). (B) In β thalassemia, there is excess α-globin formation due to decreased or absent β-globin production. The excess α-globin precipitates in the cells and on membranes and leads to ineffective erythropoiesis in nucleated red cells in the bone marrow and red cell hemolysis in circulating blood cells. In the absence of AHSP, the anemia is worse because of the further destabilization of the excess α-globin (not shown). (C) In this issue of the JCI, Yu et al. (11) show that in mice with α thalassemia, there is an excess of β-globin chains due to a deficiency of α-globin, and mild anemia. In α thalassemia in the absence of AHSP, β-globin precipitates in red cell membranes, presumably because the α-globin–AHSP complex is a required intermediate for optimal HbA formation.