Schematic representation of the role of RSP2 in the development of severe anemia during P falciparum infection. RSP2 transferred to the surface of UEs during invasion failure or to IEs after delayed invasion is recognized by antibodies, leading to its elimination by 3 different mechanisms. RSP2⁺ erythrocytes tagged with opsonizing antibodies are destroyed by phagocytosis. These antibodies activate complement, which induces the lysis of RSP2⁺ erythrocytes. RSP2 may induce the rigidification of RSP2⁺ erythrocytes in the presence or absence of antibodies, resulting in their destruction in the spleen. RSP2 is involved in the dyserythropoiesis observed in severe anemia. RSP2 is transferred to the surfaces of erythroid precursors because of the presence of receptors such as GA, facilitating interaction with merozoites. From the erythroid blast-forming unit (BFU-E) or CFU-E stage after the transfer of RSP2, precursor cells may be modified by the combined action of opsonizing antibodies and complement.