Plasmodium falciparum histidine-rich protein II (PfHRP2)

Plasmodium falciparum histidine-rich protein II (PfHRP2) is a unique, highly abundant antigen released by *P. falciparum*-infected erythrocytes during the blood stage of malaria[1][2][3]. Structurally, it is distinguished by its high histidine content (~35%), a large number of histidine-alanine tripeptide repeats, and strong affinity for heme and metal ions such as Zn2+[1][3][4]. PfHRP2 participates in parasite heme detoxification and hemozoin formation; it also modulates coagulation by binding glycosaminoglycans and inhibiting antithrombin, potentially promoting vascular microblockade and organ failure in severe malaria[1]. PfHRP2 forms heme-laden nanoparticles capable of overwhelming host endothelial cells with iron and inducing reactive oxygen species, which result in vascular leakage and contribute to cerebral malaria[3]. Clinically, PfHRP2 is the primary marker used in rapid diagnostic testing for *P. falciparum* infection, though gene deletions in some parasite populations can reduce test reliability[4][5]. No drugs target PfHRP2 directly, but its role in severe malaria is under investigation for adjunctive therapies focused on its pathogenic mechanisms rather than as a druggable molecular target[3].

Other names

HRPIIPfHRP-IIhistidine-rich protein IIP. falciparum HRP2PfHRP2 antigen

Not applicable for therapy; however, drugs and molecules under investigation include heme chelators and inflammasome inhibitors that can disrupt pathological effects of PfHRP2:heme nanoparticles