LAUSR

Malaria disease kills > 400,000 people every year, and Plasmodium falciparum is the causative agent of this severe disease (World Health Organization, 2021). The P. falciparum has a complex life cycle involving sexual reproduction in a mosquito vector and asexual replication in the human host cells (Maier et al., 2019). The asexual stage is the most critical since patients start showing clinical symptoms at this stage, such as fever, jaundice, severe anemia, renal failure, and cerebral malaria, leading to death (Miller et al., 2002). These symptoms are triggered by the erythrocyte rupture during asexual multiplication. Within the erythrocyte, the P. falciparum parasite goes through various stages: ring, trophozoite, and schizont. Finally, the mature schizont releases 16–32 daughter merozoites after erythrocyte rupturing into the blood circulation to invade new erythrocytes (Bannister et al., 2000). Although the blood-stage parasites account for the clinical manifestations of malaria, the erythrocyte environment is not suitable for parasite growth and asexual replication due to limited nutrients, inhospitable ionic composition, or acidic pH. To overcome these constraints, the effector proteins are exported by the malaria parasite into the host cell cytoplasm and membrane surface (Maier et al., 2009; Mundwiler-Pachlatko and Beck, 2013; Spillman et al., 2015; Sherling and van Ooij, 2016). With these effector proteins, the parasite alters the host cell physiology to fit its growth, extends its communication to the extracellular environment, and facilitates its immune evasion. The surface-exposed effector proteins (SEPs) attracted a huge amount of attention based on their functions and potential as drug targets. For example, the P. falciparum erythrocyte membrane protein 1 (PfEMP1) is well known for its crucial role in cytoadherence, mediating parasite virulence (Peters et al., 2007; Zhang et al., 2011; McMillan et al., 2013; Lee et al., 2019); the subtelomeric variable open reading frame proteins (STEVORs) and the repetitive interspersed family proteins (RIFINs) facilitate the adhesion to the endothelial lining of capillaries, evasion from splenic filtration, and possibly in antigenic variation (Wahlgren et al., 2017); and the cytoadherencelinked asexual gene proteins (CLAGs) contribute to the plasmodial surface anion channel (PSAC), which is functional for nutrient uptake and membrane permeability (Nguitragool et al., 2011; Desai, 2014). However, the identification and determination of SEPs are still not straightforward, even after their importance has been recognized and confirmed for decades. The main challenges of SEP