UPK1B (uroplakin 1B) is a tetraspan membrane protein predominantly expressed in terminally differentiated urothelial cells, where it localizes to the apical membrane as a component of urothelial plaques 1. Its primary function is to stabilize epithelial cells lining the bladder and provide a barrier function to prevent urine passage across the urothelium 21. UPK1B contributes to normal bladder epithelial physiology by regulating membrane permeability and maintaining apical membrane integrity through interactions with the cytoskeleton. In malignant contexts, UPK1B expression is frequently dysregulated. It is highly expressed in urothelial carcinomas (58-95% positivity), but paradoxically, low UPK1B expression correlates with high-grade, invasive tumors and lymph node metastasis in bladder cancer 23. UPK1B also promotes invasion and metastasis in bladder cancer by activating the Wnt/β-catenin signaling pathway 4, and enhances non-small cell lung cancer progression through the c-myc/Sox4 axis 5. Clinically, UPK1B serves as a valuable diagnostic immunohistochemical marker to distinguish urothelial carcinomas from other malignancies, including lung and prostatic adenocarcinomas 26. Loss of UPK1B expression during tumor stage progression provides prognostic information, particularly in advanced disease 3.