Upk1b, encoding Uroplakin 1B, is a gene crucial for the stability and strengthening of epithelial cells lining the bladder. Uroplakins, a family of membrane-spanning proteins, are highly specific to the urothelium. They form urothelial plaques in the apical membrane of umbrella cells, providing a barrier to prevent urine passage across the urothelium in the renal pelvis, ureters, and bladder. They are also involved in nephrogenesis [7].

In urothelial carcinoma of the bladder, a progressive loss of Upk1b expression is linked to stage progression. Low Upk1b expression is associated with high-grade, invasive tumor growth, and nodal metastasis [5,6]. In other cancers, such as non-small cell lung cancer, Upk1b promotes cell invasion and stem-cell characteristics by modulating the c-myc/Sox4 axis [1]. In bladder cancer, it promotes invasion and metastasis via regulating the Wnt/β-catenin pathway [2]. In renal cell carcinoma, NAA10 promotes cancer cell proliferation by upregulating Upk1b [3]. In gastric cancer, Upk1b is upregulated, promoting tumor progression, and is associated with distant metastasis [4,8].

In conclusion, Upk1b plays essential roles in maintaining the normal function of the urinary tract epithelium and is involved in the development and progression of multiple cancers. Studies on Upk1b knockout or conditional knockout models in mice could potentially further our understanding of its functions in normal physiological processes and disease conditions, providing potential targets for cancer diagnosis, prognosis, and treatment.