Tamm–Horsfall protein or uromodulin: new ideas about an old molecule

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Abstract
More than 50 years ago, Tamm and Horsfall isolated a mucoprotein from the human urine, and showed that the protein was able to interact and inhibit viral haemagglutination [1,2]. Of interest, the protein was found to be heavily glycosylated, containing up to 30% of its mass in carbohydrates [3]. It was then discovered that the Tamm–Horsfall protein (THP), as it was readily named, was the most abundant protein in normal human urine, with a migration pattern at ∼90 kDa in SDS–PAGE [4]. In 1985, Muchmore and Decker [5] identified a 85 kDa glycoprotein in the urine of pregnant women. The protein was named uromodulin, due to its potent immunosuppressive activity reflecting its ability to inhibit antigen-induced T-cell proliferation and monocyte cytotoxicity in vitro [5]. Besides the molecular mass and the abundance in urine, the characterization of uromodulin revealed a number of resemblances with THP, including a ∼30% carbohydrate content, a tendency to form aggregates and a significant number of intrachain disulfide bridges [5]. Based on sequence analysis, Pennica et al. [6] later confirmed that uromodulin was indeed THP. For the sake of clarity, we will use the term uromodulin to discuss the THP/uromodulin protein in this review.