Plasmodium falciparum Niemann-Pick type C1-related protein (PfNCR1)

Plasmodium falciparum Niemann-Pick type C1-related protein (PfNCR1) is an essential membrane transporter localized to the plasma membrane of the malaria parasite Plasmodium falciparum. It plays a critical role in maintaining membrane lipid composition, particularly by shuttling cholesterol between different compartments within the parasite. Structural studies have revealed that PfNCR1 contains distinct binding sites for cholesterol and forms a tunnel-like structure facilitating its export from the parasite plasma membrane to the parasitophorous vacuole, which is vital for parasite survival during its asexual blood stage. PfNCR1 has been validated as a druggable antimalarial target. Inhibitors such as MMV009108 block this transporter, leading to disruption of membrane homeostasis and increased sensitivity of parasites to saponin—ultimately resulting in their death. The essentiality and lack of close human orthologs make it an attractive candidate for therapeutic intervention against malaria.

Other names

NCR1PFA0375cPF3D7_0107500

Inhibition of PfNCR1 blocks cholesterol transport and disrupts membrane homeostasis in the parasite