PfRh

PfRH, short for Plasmodium falciparum reticulocyte-binding protein homolog, refers to a family of merozoite surface and rhoptry proteins that function as invasion ligands during the entry of Plasmodium falciparum into human red blood cells. The PfRH family includes several members, notably PfRH1, PfRH2a, PfRH2b, PfRH4, and PfRH5. These proteins are secreted during merozoite development and invasion and, in many parasite strains, contribute to alternative pathways that allow invasion even when other ligands are blocked or receptors are altered.

PfRH5 is the best characterized member and is unusual in being essential for invasion across strains. It binds the erythrocyte receptor basigin (CD147) and forms a trimeric complex with PfCyRPA and PfRipr that is required for productive entry. Other PfRH proteins, such as PfRH1, PfRH2a/2b, and PfRH4, mediate receptor-dependent adhesion that can be neuraminidase-sensitive or neuraminidase-resistant, enabling the parasite to switch invasion routes in response to host receptor variation or immune pressure.

Genetically, PfRH genes show considerable diversity among parasite isolates, though PfRH5 is relatively conserved, making it a focal point for vaccine research. The PfRH family is studied alongside the EBL (erythrocyte binding-like) ligands as part of the parasite’s redundant toolkit for red blood cell invasion, contributing to the resilience and adaptability of Plasmodium falciparum.