SLCO1B1 and cancer: Compared to lipophilic estrone and estradiol, the estrogen ester and conjugate, E3S, is unable to permeate through cell membranes and is transported mainly via OATPs, which has been widely used as a prototypical model substrate of OATP1B1.43–45 Inhibitors of OATPs are of interest in treating estrogen-associated cancers.46 In our study, the cryo-EM structures of OATP1B1–E unexpectedly revealed three different conformations: inward-open state with high resolution, outward-open and occluded states with moderate to low resolutions (Fig. 4a).