{"entity":{"id":"nis-symporter","kind":"target","name":"NIS (sodium-iodide symporter)","aka":["Sodium/iodide cotransporter","SLC5A5"],"tldr":"A protein in the thyroid that pulls iodine out of the blood to make thyroid hormone. It is the reason radioactive iodine can find and treat thyroid cancer almost anywhere in the body.","summary":"NIS is a 13-transmembrane-domain glycoprotein on the basolateral membrane of thyroid follicular cells that actively co-transports two sodium ions with one iodide ion, using the electrochemical sodium gradient generated by Na+/K+-ATPase, as the first step of thyroid hormone synthesis. Its expression in the thyroid is driven by thyroid-stimulating hormone (TSH) acting through the cAMP pathway, which is why thyroid-stimulating hormone withdrawal or recombinant human TSH (thyrotropin alfa) is used clinically to maximise iodide uptake before radioiodine scanning or therapy.\n\nMore than 70% of differentiated (papillary and follicular) thyroid cancers retain enough NIS expression to concentrate iodide, which is the biological basis of whole-body radioiodine scanning and I-131 therapy for remnant ablation and metastatic disease. NIS is also expressed, at lower levels, in several extrathyroidal tissues: salivary glands, gastric mucosa, lactating breast, lacrimal glands, choroid plexus and placenta. Uptake in salivary glands and stomach is well below thyroid levels and the absorbed dose in these tissues is small relative to the thyroid, but it is still the mechanism behind the sialadenitis (dry mouth, taste change) and, less often, gastritis seen after high-activity I-131 therapy.\n\nAs a target, NIS is close to ideal for differentiated thyroid cancer: high density, non-internalising simple ion transport, and near-total tissue restriction outside a few low-uptake sites. Its main practical limitation is that a minority of thyroid cancers dedifferentiate and lose NIS expression (radioiodine-refractory disease), and normal-tissue uptake in salivary gland and stomach still causes most of the non-thyroid toxicity of I-131 therapy.","asOf":"2026-09-22","links":[{"label":"PMC: modulation of NIS expression in salivary gland tissue and I-131 uptake","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3752512/"},{"label":"PMC: the sodium iodide symporter (NIS) - regulation and approaches to therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3408573/"},{"label":"PMC: sodium/iodide symporter - molecular physiology and preclinical applications (tissue distribution table)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5739519/"},{"label":"MedlinePlus Genetics: SLC5A5 gene","url":"https://medlineplus.gov/genetics/gene/slc5a5/"}],"tags":["thyroid","ion transporter","theranostics"],"related":["radioactive-iodine","radioiodine-therapy","thyroid","thyrotropin-alfa","radioiodine-term","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC5A5","biology":"A basolateral membrane glycoprotein that actively co-transports two sodium ions with one iodide ion into thyroid follicular cells, the first step of thyroid hormone synthesis, driven by TSH via the cAMP pathway. Because most differentiated thyroid cancer retains this transporter, it is the biological basis for diagnostic and therapeutic use of radioactive iodine.","whereFound":["Thyroid follicular cells: high, TSH-driven expression; basis of normal thyroid hormone synthesis","Differentiated thyroid cancer: retained in >70% of papillary and follicular carcinomas","Salivary gland striated ducts: moderate expression, clinically relevant because of I-131 sialadenitis","Gastric mucosa (basolateral): moderate expression, secretes iodide into gastric juice","Lactating mammary gland, lacrimal gland, choroid plexus, placenta: lower-level physiological expression"],"targetClass":"other","prevalence":[]},"route":"/targets/nis-symporter/","neighbours":{"drug":[{"id":"radioactive-iodine","kind":"drug","name":"Radioactive iodine (I-131)","route":"/drugs/radioactive-iodine/"},{"id":"thyrotropin-alfa","kind":"drug","name":"Thyrotropin alfa","route":"/drugs/thyrotropin-alfa/"}],"technology":[{"id":"radioiodine-therapy","kind":"technology","name":"Radioiodine therapy and whole-body iodine scanning","route":"/technologies/radioiodine-therapy/"}],"indication":[{"id":"thyroid","kind":"indication","name":"Thyroid cancer","route":"/indications/thyroid/"}],"term":[{"id":"radioiodine-term","kind":"term","name":"Radioiodine therapy (I-131)","route":"/terms/radioiodine-term/"}],"isotope":[{"id":"i-131","kind":"isotope","name":"Iodine-131","route":"/isotopes/i-131/"}]}}