The working lives of neuronal 5-HT_2A receptors from the outside in

5-HT_2A receptors have been shown to play critical roles in regulating neuronal signalling networks and brain plasticity. They have become important targets for treatment of resistant forms of mental health disorders such as depression, anxiety and post-traumatic stress disorder. Like many G protein-coupled receptors (GPCRs), signalling downstream of 5-HT_2A depends on where the receptor is in the cell. Events and signalling pathways modulated by the cell surface pool of receptors may be distinct from those regulated by an internal pool of receptors. In this review, we parse out how the cell organizes and regulates this location bias and explore approaches to target the distinct receptor pools pharmacologically.