Uromodulin (also known as Tamm–Horsfall protein) is a kidney-specific glycoprotein secreted bidirectionally into urine and into the circulation, and it is the most abundant protein in normal urine. Although the discovery of uromodulin predates modern medicine, its significance in health and disease has been rather enigmatic. Research studies have gradually revealed that uromodulin exists in multiple forms and has important roles in urinary and systemic homeostasis. Most uromodulin in urine is polymerized into highly organized filaments, whereas non-polymeric uromodulin is detected both in urine and in the circulation, and can have distinct roles. The interactions of uromodulin with the immune system, which were initially reported to be a key role of this protein, are now better understood. Moreover, the discovery that uromodulin is associated with a spectrum of kidney diseases, including acute kidney injury, chronic kidney disease and autosomal-dominant tubulointerstitial kidney disease, has further accelerated investigations into the role of this protein. These discoveries have prompted new questions and ushered in a new era in uromodulin research. Here, we delineate the latest discoveries in uromodulin biology and its emerging roles in modulating kidney and systemic diseases, and consider future directions, including its potential clinical applications.

尿调节蛋白（也称为 Tamm-Horsfall 蛋白）是一种肾脏特异性糖蛋白，双向分泌到尿液和循环中，是正常尿液中最丰富的蛋白质。尽管尿调节素的发现早于现代医学，但它在健康和疾病中的重要性一直相当神秘。研究逐渐揭示，尿调节蛋白以多种形式存在，在尿液和全身稳态中起重要作用。尿液中的大多数尿调节蛋白聚合成高度组织化的细丝，而非聚合物尿调节蛋白在尿液和循环中都检测到，并且可以具有不同的作用。尿调节蛋白与免疫系统的相互作用最初被报道为这种蛋白质的关键作用，现在人们更好地理解了。此外，尿调节蛋白与一系列肾脏疾病有关的发现，包括急性肾损伤、慢性肾病和常染色体显性肾小管间质性肾病，进一步加速了对这种蛋白质作用的研究。这些发现引发了新的问题，并开创了尿调节蛋白研究的新时代。在这里，我们描述了尿调节蛋白生物学的最新发现及其在调节肾脏和全身性疾病中的新兴作用，并考虑了未来的方向，包括其潜在的临床应用。