Thyroid hormones are essential for brain development. The active thyroid 
hormone, T3, binds to several products of two genes, the nuclear thyroid hormone 
receptors alpha and beta, and thus regulates gene expression. Mutations in a 
thyroid hormone transmembrane transport protein, monocarboxylate transporter 8 
(MCT8), underlie one of the first described X-linked mental retardation 
syndromes, the Allan-Herndon-Dudley syndrome. This discovery sparked great 
interest in the process of thyroid hormone transmembrane transport. 
Iodothyronines are charged amino acid derivatives and require protein 
facilitators to cross cellular membranes. Thyroid hormones are translocated 
across lipid bilayers by several members of the major facilitator superfamily, 
including monocarboxylate transporters, amino acid transporters, and organic 
anion transporting polypeptides. Although until recently few researchers 
considered thyroid hormone transporters an important object of study, there is 
now a large number of candidate transporters to be reckoned with in the brain. 
Moreover, to finally cross the neuronal plasma membrane, any iodothyronine 
molecule on its way toward a neuronal nucleus has to cross consecutively the 
lumenal and ablumenal membranes of the capillary endothelium, enter astrocytic 
foot processes, and leave the astrocyte through the plasma membrane. Moreover, 
microglia, oligodendrocytes, and precursor and stem cells are thyroid hormone 
responsive and likely express thyroid hormone transporters. Hence, the many 
roles played by thyroid hormones in the development, function, and regeneration 
of the nervous system are dependent on the spatiotemporal expression of several 
transmembrane transport proteins.