The present Research Topic aims to provide updated reviews on TSH receptor structure and function, and its relationship with thyroid autoimmunity. Indeed, original reviews deal also with the pathogenesis of Graves' disease and its complications such as thyroid-associated opthalmopathy. Another issue that is addressed in this topic is the multifaceted nature of TSH receptor autoantibodies (TRAbs) and their role in the diagnosis and prognosis of Graves’ disease, with the most recent data on the clinical applications of TRAbs assays. Furthermore, the functional role of the TSH receptor in extrathyroidal tissues is discussed.