Thyroid hormones are essential for normal development and metabolism. Thyroid 
hormone biosynthesis requires iodide uptake into the thyrocytes and efflux into 
the follicular lumen, where it is organified on selected tyrosyls of 
thyroglobulin. Uptake of iodide into the thyrocytes is mediated by an intrinsic 
membrane glycoprotein, the sodium-iodide symporter (NIS), which actively 
cotransports two sodium cations per each iodide anion. NIS-mediated transport of 
iodide is driven by the electrochemical sodium gradient generated by the 
Na(+)/K(+)-ATPase. NIS is expressed in the thyroid, the salivary glands, gastric 
mucosa, and the lactating mammary gland. TSH and iodide regulate iodide 
accumulation by modulating NIS activity via transcriptional and 
posttranscriptional mechanisms. Biallelic mutations in the NIS gene lead to a 
congenital iodide transport defect, an autosomal recessive condition 
characterized by hypothyroidism, goiter, low thyroid iodide uptake, and a low 
saliva/plasma iodide ratio. Pendrin is an anion transporter that is 
predominantly expressed in the inner ear, the thyroid, and the kidney. Biallelic 
mutations in the SLC26A4 gene lead to Pendred syndrome, an autosomal recessive 
disorder characterized by sensorineural deafness, goiter, and impaired iodide 
organification. In thyroid follicular cells, pendrin is expressed at the apical 
membrane. Functional in vitro data and the impaired iodide organification 
observed in patients with Pendred syndrome support a role of pendrin as an 
apical iodide transporter.