The molecular defect involves the genes coding for RBC membrane proteins ANK1 (ankyrin, 50–60% of HS patients), SPTA1 or SPTB (α- or β-spectrin, 20% of HS, taken together), SLC4A1 (band 3, 15–20% of cases), and EPB42 (protein 4.2), the latter being mutated in autosomal recessive HS, more common in Japan but rarer in other populations (Table 1). This evidence concerns the gene SPTB and histiocytic sarcoma.