“…A key goal is to identify GPCRs that are important for cellular function and that may be therapeutic targets. The use of RNA interference and gene editing approaches (i.e., CRISPR/Cas9) to knock down receptor expression in cells of interest and then to assess the impact of receptor knock down on functional activity (signal transduction or cellular responses) provides a way to survey a population of GPCRs and identify physiologically (and potentially pharmacologically) important GPCRs (Willets and Nash, 2013). Additional features to help such prioritization include 1) the level of expression (more highly expressed GPCRs are predicted to contribute to a greater extent to cell function and may be easier to study); 2) knowledge of other cell types that express receptors of potential interest [to achieve greater selectivity in the site of action, including by comparing expression in cells that are related to one another, such as, for example, in different types of macrophages (Lattin et al, 2008;Groot-Kormelink et al, 2012;Hohenhaus et al, 2013)]; 3) choosing GPCRs whose expression is shared in a cell type found in humans and experimental animals (e.g., mice, rats); and 4) availability of reagents Assessing GPCR Expression in Native Cells (e.g., agonists, antagonists, antibodies) to conduct signaling and functional studies.…”