The role of PfEMP1 adhesion domain classification in Plasmodium falciparum pathogenesis research

•The PfEMP1 protein family is a major virulence determinant for P. falciparum.•PfEMP1 size and sequence polymorphism obscures binding patterns.•Domain classification can predict binding and protein functional specialization.•Classification provides a framework to gain molecular insight into severe malaria. The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family has a key role in parasite survival, transmission, and virulence. PfEMP1 are exported to the erythrocyte membrane and mediate binding of infected erythrocytes to the endothelial lining of blood vessels. This process aids parasite survival by avoiding spleen-dependent killing mechanisms, but it is associated with adhesion-based disease complications. Switching between PfEMP1 proteins enables parasites to evade host immunity and modifies parasite tropism for different microvascular beds. The PfEMP1 protein family is one of the most diverse adhesion modules in nature. This review covers PfEMP1 adhesion domain classification and the significant role it is playing in deciphering and deconvoluting P. falciparum cytoadhesion and disease.