Thyroid hormones (THs), thyroxine (T4), and triiodothyronine (T3), regulate growth, metabolism, and neurodevelopment. THs secretion is controlled by the pituitary thyroid-stimulating hormone (TSH) and the hypothalamic–pituitary–thyroid (HPT) axis. The organic anion-transporting polypeptide 1C1 (OATP1C1/SLCO1C1) and the monocarboxylate transporter 8 (MCT8/SLC16A2) actively transport THs, which bind to their nuclear receptors and induce gene expression. A mutation in OATP1C1 is associated with brain hypometabolism, gradual neurodegeneration, and impaired cognitive and motor functioning in adolescent patients. To understand the role of Oatp1c1 and the mechanisms of the disease, we profiled the transcriptome of oatp1c1 mutant ( oatp1c1 −/−) and mct8 −/− xoatp1c1 −/− adult male and female zebrafish brains. Among dozens of differentially expressed genes, agouti-related neuropeptide 1 ( agrp1 ) expression increased in oatp1c1 −/− adult brains. Imaging in the hypothalamus revealed enhanced proliferation of Agrp1 n...