Thyroid hormone transport into cells critically depends on plasma membrane transport proteins. One of these, monocarboxylate transporter 8 (MCT8), is mutated in patients suffering from a form of X-linked mental retardation, the Allan-Herndon-Dudley syndrome. These patients are characterized by abnormal thyroid hormone and TSH plasma levels indicating a role for MCT8 in the regulation of the thyroid hormone axis. Mice lacking the Mct8 gene replicate the thyroid hormone abnormalities observed in the human patients. However, no neurological deficits have been described in Mct8-deficient mice. We have subjected Mct8-deficient mice to a comprehensive immunohistochemical, neurological, and behavioral screen. Unlike earlier reports, we have found several behavioral abnormalities in Mct8 mutant animals. Aspects of the behavioral phenotype are both compatible with alterations observed in hypothyroidism and hyperthyroidism. We thus hypothesized that in Mct8-mutant mice, subsets of neurons exist in a hyperthyroid and hypothyroid state, respectively. In order to analyze this discrepancy, we characterized thyroid hormone transporters expressed in mouse cortical neurons using pharmacological tools and identified the T3 transporters expressed by mRNA analysis. Among the T3 transporters expressed in primary cortical neurons, Lat2, a L-type amino acid transporter, was co-expressed with Mct8 both in isolated neurons and in the mouse brain during development. In contrast, LAT2 is expressed in human brain during gestation, but in a spatio-temporal pattern not overlapping with MCT8. We speculate that lack of functional complementation by LAT2 in developing human neurons may precipitate the devastating neurodevelopmental phenotype in MCT8-deficient patients, while Mct8-deficient mouse neurons are functionally complemented by Lat2.