Uromodulin (also known as Tamm-Horsfall protein) is exclusively produced in the kidney and is the most abundant protein in normal urine. The function of uromodulin remains elusive, but the available data suggest that this protein might regulate salt transport, protect against urinary tract infection and kidney stones, and have roles in kidney injury and innate immunity. Interest in uromodulin was boosted by genetic studies that reported involvement of the UMOD gene, which encodes uromodulin, in a spectrum of rare and common kidney diseases. Rare mutations in UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD), which leads to chronic kidney disease (CKD). Moreover, genome-wide association studies have identified common variants in UMOD that are strongly associated with risk of CKD and also with hypertension and kidney stones in the general population. These findings have opened up a new field of kidney research. In this Review we summarize biochemical, physiological, genetic and pathological insights into the roles of uromodulin; the mechanisms by which UMOD mutations cause ADTKD, and the association of common UMOD variants with complex disorders.

尿调节蛋白（也称为Tamm-Horsfall蛋白）仅在肾脏中产生，是正常尿液中含量最丰富的蛋白。尿调节蛋白的功能仍然难以捉摸，但是现有数据表明该蛋白可能调节盐的转运，防止尿路感染和肾结石，并在肾脏损伤和先天免疫中起作用。遗传研究增加了对尿调节蛋白的兴趣，该研究报道了编码尿调节蛋白的UMOD基因参与了一系列罕见和常见的肾脏疾病。UMOD中的罕见突变会导致常染色体显性遗传性肾小管间质性肾脏疾病（ADTKD），从而导致慢性肾脏疾病（CKD）。此外，全基因组关联研究已经确定了UMOD中的常见变体在一般人群中，它们与CKD的风险，高血压和肾结石的发生密切相关。这些发现开辟了肾脏研究的新领域。在本综述中，我们总结了对尿调节素作用的生化，生理，遗传和病理学见解；UMOD突变导致ADTKD的机制，以及常见UMOD变体与复杂疾病的关联。