Heterologously expressed targets in stable cell lines are powerful tools for discovering small molecule and antibody drug leads. Assays from these cell lines are robust, reliable and target-specific. Before moving drug candidates into animal models and human trials, translational in vitro assays are much desired intermediate steps. These assays utilize endogenously expressed targets in physiologically relevant cells. However, the challenge is target-specificity. Since related proteins from the same family as the target of interest may signal in the same pathways, the results can be confounding from these native cells. This is where gene-editing is needed.