Plasmodium falciparum replicate in liver cells, are released and invade erythrocytes. However, infected erythrocytes are destroyed as they pass through the spleen. How does the plasmodium-infected red cell escape destruction? It does this by synthesizing a protein called Plasmodium Falciparum Erythrocyte Membrane Protein-1 (PfEMP1) which by some unknown mechanism is expressed on the surface of the infected erythrocyte. This protein acts as an anchor that attaches the infected erythrocyte to the epithelial cells of the wall of the blood vessels. This can lead to obstruction of blood vessels, particular in the brain.

PfEMP1 elicits the expression of antibodies in the infected patient which can destroy the infected red cells. To avoid this fate, the parasite has about 60 var genes that can express 60 variants of PfEMP1. At one time only one var gene is transcribed and translated into protein (mutually exclusive transcription). This is very similar to the multitude of variable surface glycoproteins expressed by some trypanosomes, though the mechanism of the sequential expression of surface antigens is different. When most (>99%) of the infected cells have been destroyed by the anti-PfEMP1 antibodies, some will have expressed a different var gene and thus will express a new surface protein that is nor recognized by antibodies elicited by the first variant. Thus, these cells escape destruction. Which PfEMP1 protein is expressed is under the control of a histone methyltransferase enzyme, PfSET10 which maintains the activity of a given var gene.