The effects of estrogen on responsive cells and organismic development have long been known and well documented. Estrogen binds to the estrogen receptor, a dimer of the complex translocates to the nucleus, binds specific DNA elements and regulates the transcription of particular genes, a process that takes some time to achieve. One of the curious findings of intense estrogen research-that some estrogen-dependent effects appear to occur immediately-has led to the conclusion that quick responses are mediated by an estrogen binding protein(s) in the cytoplasm or located at the plasma membrane. Hasbi et al. chart the course through which several characterized estrogen binding proteins (not necessarily sharing sequence similarity beyond the estrogen binding domain) were discovered, including most notably, the orphan G protein-coupled receptor GPR30. And what is to be made of differing accounts of GPR30's intracellular whereabouts?