UPK1A (uroplakin 1A) is a membrane-spanning protein that serves as a critical structural component of the asymmetric unit membrane in terminally differentiated urothelial cells 1. It localizes to the apical membrane of umbrella cells, where it associates into urothelial plaques to provide a barrier function preventing urine passage across the urothelium 1. UPK1A helps stabilize and strengthen epithelial cells during bladder distension 2, potentially through regulating membrane permeability and apical membrane stabilization via cytoskeletal interactions. Mechanistically, UPK1A interacts with regucalcin and proteasome subunit beta 1, suggesting roles in protein degradation and spermatogenesis 3. In cancer contexts, UPK1A functions as a tumor suppressor: ectopic expression inhibits cell proliferation, migration, and invasion through β-catenin pathway inactivation 4, while knockdown suppresses proliferation and enhances apoptosis in bladder cancer cells 5. Clinically, UPK1A serves as a diagnostic marker for urothelial carcinoma, showing 42.6-98% positivity across urothelial tumor subtypes 2. However, its diagnostic sensitivity decreases in muscle-invasive cancers (41.5%) due to expression loss during grade and stage progression 26. Reduced UPK1A expression correlates with poor prognosis in gastric adenocarcinoma 7 and esophageal squamous cell carcinoma 4, making it an independent prognostic biomarker.