Sodium-transporting ATPase 4 (PfATP4) (PfATP4)

Plasmodium falciparum P-type Na+-ATPase (PfATP4) is a vital membrane-bound enzyme located on the plasma membrane of the malaria parasite during its erythrocytic stage. Its primary biological function is to export sodium ions (Na+) from the parasite's cytosol to the host environment, maintaining a low intracellular sodium concentration essential for survival (UniProt Q8I6R7). This pump also plays a secondary role in regulating the parasite's internal pH and osmotic pressure (PubMed: 23940340). Because PfATP4 is structurally distinct from human sodium pumps, it has emerged as a high-priority target for next-generation antimalarial drugs, such as the spiroindolone Cipargamin (KAE609) (PubMed: 20813920). Inhibition of PfATP4 causes a rapid, lethal accumulation of sodium within the parasite, leading to cellular swelling and lysis. While highly effective in clearing parasites quickly, the target is prone to point mutations in the pfatp4 gene that can confer drug resistance, necessitating its use in combination therapies to ensure long-term efficacy.

Other names

PfATP4Sodium-transporting ATPase 4P-type sodium pumpP-type Na+-ATPase

Inhibition of the PfATP4 pump leads to a rapid increase in intracellular sodium concentration within the parasite, resulting in osmotic swelling, disruption of pH homeostasis, and ultimately parasite death (PubMed: 23940340).