PfRH4

PfRH4 (reticulocyte-binding protein homolog 4) is a member of the PfRh family of merozoite surface proteins in Plasmodium falciparum. Like other PfRh proteins, PfRH4 is expressed on the surface of the merozoite and contributes to the parasite’s ability to invade human red blood cells. It is associated with invasion pathways that can function independently of sialic acid–dependent receptors, providing redundancy when sialic acid–dependent routes are unavailable or blocked.

The exact erythrocyte receptor for PfRH4 has not been definitively identified. Some studies have suggested potential interactions with complement receptor 1 (CR1) or other surface molecules, but the receptor remains incompletely characterized. PfRH4 function appears to be partly strain-dependent, reflecting the diversity and redundancy within the PfRh gene family.

PfRH4 is part of a multigene family located in subtelomeric regions of the parasite genome; these genes show high allelic diversity and differential expression across strains. Expression is typically associated with late schizogony and merozoite formation, with the protein trafficked to the merozoite surface prior to invasion.

In vitro studies have shown that antibodies against PfRh family proteins can inhibit invasion in certain contexts, underscoring PfRH4’s role in merozoite entry and its potential relevance to vaccine strategies. However, PfRH4 is less well characterized than some family members, and its exact contribution to invasion may vary by strain and host receptor availability.