Similar to PfMDR1, PfCRT is localized to the DV membrane and is a polytopic, integral membrane protein that is likely to perform some type of transport function [21, 22, 55, [71] [72] [73] [74] [75] [76] . Similar to the case for HsMDR1 most initial hypotheses for its function suggest either ion or drug transport or both, since, again, CQR parasites accumulate less antimalarial drug in a given time relative to CQS and quinolinal antimalarial drugs (like anti-tumor drugs), which are hydrophobic weak bases. In fact, CQ and related drugs are dibasic and the DV is now known to be quite acidic. So, fold concentration of CQ within the DV (where the heme-drug target is found) is dependent upon the square of the net pH gradient and would be as much as 10 5 -10 6 -fold by the predictions of weak base partitioning theory, depending on relative permeabilities of neutral, +1 and +2 CQ species [6]. Thus, even very subtle changes in DV pH would have very significant consequences. Progress on these and related questions is summarized later.