Plasmodium falciparum cyclic amine resistance locus protein (PfCARL) (PfCARL)

The Plasmodium falciparum cyclic amine resistance locus protein (PfCARL) is a conserved, essential membrane protein localized to the endoplasmic reticulum (ER) of the malaria parasite (UniProt Q8I5U1). It was first identified as a multi-drug resistance locus through in vitro evolution studies using imidazolopiperazines and triaminopyrimidines (LaMonte et al., 2014, Nature). While its precise biochemical function remains under investigation, evidence suggests PfCARL plays a critical role in protein folding, quality control, or the trafficking of proteins from the ER to other organelles. Mutations in the pfcarl gene are a primary mechanism of resistance against several clinical-stage antimalarial candidates, most notably Ganaplacide (KAF156). Because PfCARL is essential for parasite survival and lacks a direct human ortholog, it is a significant focus for the development of next-generation antimalarials and the monitoring of drug resistance in endemic regions (Lim et al., 2016, mBio).

Other names

PfCARLPF3D7_0321900CARLCyclic amine resistance locus protein

Drugs targeting or interacting with PfCARL are thought to disrupt essential protein trafficking or folding processes within the parasite's endoplasmic reticulum, leading to proteostatic stress and parasite death (LaMonte et al., 2014, Nature).