P-type sodium-transporting ATPase 4 (PfATP4)

Plasmodium falciparum P-type ATPase 4 (PfATP4) is a vital sodium-efflux pump located on the plasma membrane of the malaria parasite. It plays a critical role in maintaining low intracellular sodium levels and regulating the parasite's internal pH and osmotic pressure [1, 3]. Because the parasite resides within a host red blood cell where sodium concentrations are high, PfATP4 must actively extrude sodium ions to prevent osmotic swelling and cellular stress [4, 9]. This transporter has emerged as a premier target for a new generation of antimalarial drugs, including spiroindolones like cipargamin and dihydroisoquinolones like SJ733 [1, 8]. Inhibition of PfATP4 leads to a rapid, lethal accumulation of sodium within the parasite, causing it to swell and eventually lyse [6, 7]. While PfATP4 is highly conserved and essential for parasite survival, the emergence of resistance-conferring mutations in the pfatp4 gene remains a significant therapeutic challenge [1, 21].

Other names

Plasmodium falciparum ATPase 4PfATP4P-type ATPase 4Sodium-efflux pumpNa+ pumpP-type cation-transporter ATPase 4ENA-type Na+-ATPase

Inhibition of Na+ efflux, leading to rapid accumulation of intracellular Na+, osmotic swelling, and parasite lysis.