Schizophrenia, affecting 20 million people worldwide, is characterised as a chronic, heterogeneous psychiatric disorder with symptoms that range from hallucinations, delusions, social withdrawal and cognitive deficits. Despite extensive study, the aetiology and pathophysiology of schizophrenia remain unknown. While current antipsychotic drugs are effective at targeting some positive symptoms (e.g. hallucinations), the cognitive deficits, which can severely impact the patient’s quality of life, are left untreated. Preclinical studies have demonstrated the antipsychotic and pro-cognitive activity of GPR52 agonists. GPR52 is an orphan GPCR that is almost exclusively expressed in the brain and has emerged as a potential target for schizophrenia. The signalling mechanisms of GPR52 at the cellular level in the context of its native environment are largely unexplored. It has been suggested that ligand-mediated receptor translocation can influence an antipsychotic drug’s clinical profile. However, for GPR52, it is unknown how our current available tool compounds mediate GPR52 intracellular trafficking. Preliminary data from my project have indicated that GPR52 ligands have different capacities to induce GPR52 translocation. In addition, the structural study of GPR52 using cryo-electron microscopy (cryo-EM) also provided insights into how these ligands bind the receptor to enhance understanding of GPR52 signalling mechanisms.