Thyroid hormone (TH) is essential for the development of virtually all tissues. The biological activity of TH is largely mediated by binding of the active hormone T3 to the nuclear T3 receptors TRá and TRâ. Three deiodinases (D1-3) and several TH transporters determine the availability of T3 for nuclear TRs. Defects in any of these proteins can have important consequences, as is illustrated by the severe psychomotor retardation in patients with inactivating mutations in MCT8, a TH transporter expressed in central neurons. This subtheme concerns the characterization of the transporters, deiodinases and TH receptors involved, the study of their regulation in ageing and disease, and the consequences of genetic variation in these TH pathway genes.