The state of the art of odorant receptor deorphanization: A report from the orphanage

The odorant receptors (ORs) provide our main gateway to sensing the world of volatile chemicals. This involves a complex encoding process in which multiple ORs, each of which detects its own set of odorants, work as an ensemble to produce a distributed activation code that is presumably unique to each odorant. One marked challenge to decoding the olfactory code is OR deorphanization, the identification of a set of activating odorants for a particular receptor. Here, we survey various methods used to try to express defined ORs of interest. We also suggest strategies for selecting odorants for test panels to evaluate the functional expression of an OR. Integrating these tools, while retaining awareness of their idiosyncratic limitations, can provide a multi-tiered approach to OR deorphanization, spanning the initial discovery of a ligand to vetting that ligand in a physiologically relevant setting.