NaISymporter

The NaI symporter, also known as the sodium/iodide symporter (NIS) and encoded by the SLC5A5 gene, is a transmembrane protein that enables active uptake of iodide into thyroid follicular cells by coupling iodide transport to the inward sodium gradient. This iodide uptake is the first essential step in thyroid hormone synthesis.

NIS functions as a secondary active transporter. It typically co-transports two Na+ ions with one I− ion from the bloodstream into the cytoplasm, making the process electrogenic. The energy for transport comes from the Na+/K+-ATPase–generated sodium gradient. Once inside the cell, iodide is moved into the apical side and into the colloid primarily via pendrin and related apical transporters, where it participates in thyroid hormone formation.

Expression of NIS is highest in the thyroid, but it is also found in other tissues, including salivary glands, lacrimal glands, gastric mucosa, placenta, and lactating mammary tissue. This distribution explains tissue-specific iodide handling and the potential for iodide uptake outside the thyroid under certain conditions.

Regulation of NIS is tightly controlled. Thyroid-stimulating hormone (TSH) is the primary regulator, upregulating NIS expression and iodide uptake through signaling pathways that increase transcription and trafficking to the basolateral membrane. Iodide excess can suppress NIS expression as part of autoregulatory mechanisms such as the Wolff-Chaikoff effect.

Clinical relevance includes congenital iodide transport defects caused by SLC5A5 mutations, which can lead to congenital hypothyroidism. NIS activity also underpins the diagnostic and therapeutic use of radioactive iodine in thyroid diseases, with uptake assays serving as important clinical tools.