NIS (sodium-iodide symporter)

NIS was molecularly cloned in 1996 by Nancy Carrasco's team, a milestone that illuminated the first step of thyroid hormone biosynthesis. It is a 13-transmembrane-domain glycoprotein encoded by the SLC5A5 gene. Transport is electrogenic and secondarily active: the Na+/K+-ATPase keeps intracellular sodium low, and that gradient powers the simultaneous entry of iodide against its own gradient.

Once inside the thyrocyte, iodine is oxidized and organified onto tyrosine residues of thyroglobulin to form T3 and T4. TSH upregulates NIS (more uptake when the body needs hormone), while chronic iodine excess inhibits it (the Wolff-Chaikoff effect).

Clinically, NIS underpins thyroid scintigraphy and radioactive iodine therapy (I-131) in hyperthyroidism and thyroid cancer: the transporter captures the isotope inside target cells. Dietary iodine deficiency, still prevalent in parts of Spain, limits the substrate available to NIS and compromises thyroid function — a risk that is especially critical during pregnancy for fetal brain development.