As mentioned previously, one additional genetic event that tailors CQ resistance caused by PfCRT, may be the mutation and/or over expression of PfMDR1, but this cannot fully explain all MDR phenotypes. Another contributing event, recently identified by QTL analysis [60] , involves one or more genes encoded by a segment of chromosome 13. This fragment is hypothesized to contain genes encoding for proteins with unclear homology to known proteins, however, it also encodes homologs to a V -type ATPase subunit and to the NHE protein family. By combining future science group QTL analysis with improved pH cyt measurements, we have recently shown that Pf NHE dysregulation is likely to be linked to one route to increased QN resistance [52] . In addition, additive QTLs on chromosomes 5 and 7 were found as expected (the identified fragments contain pfcrt and pfmdr1) [60] . Pairwise effects were also detected between chromosome 13 and a chromosome 9 locus. The NHE homolog encoded within chromosome 13 was named PfNHE1. This protein is the second largest eukaryotic NHE yet identified (surpassed only by a NHE for the related apicomplexan Toxoplasma gondii), and has several unusual features. Bioinformatic ana lysis and cross reactivity with anti-TgNHE antibody [Chen D, Pleeter P, Roepe PD, Unpublished Data] show that PfNHE is localized to the plasma membrane. Polymorphisms that encode variable DNNND repeats in the predicted PfNHE protein sequence have been found in progeny of a CQS × CQR cross, as well as a range of field isolates and additional laboratory strains showing variable QN resistance [60] .