Uroplakins

Uroplakins are a family of highly glycosylated membrane proteins that form specialized plaques in the apical surface of umbrella cells lining the urinary bladder and parts of the urethra. These plaques, also known as urothelial plaques or asymmetric unit membranes, provide a rigid barrier against the toxic effects of urine and contribute to the bladder’s remarkable stretchability during filling and emptying cycles.

Four major uroplakin isoforms have been identified in mammals: Uroplakin Ia (UPK1A), Uroplakin Ib (UPK1B), Uroplakin II (UPK2) and Uroplakin IIIa (UPK3A). The proteins assemble in heterodimeric pairs (UPK1A/UPK2 and UPK1B/UPK3A) within the endoplasmic reticulum, then traffic to the Golgi apparatus where they undergo extensive N‑linked glycosylation. Subsequent oligomerization yields hexagonal arrays that are inserted into the apical plasma membrane, forming the characteristic crystalline plaques.

Uroplakins play a critical role in maintaining urothelial integrity, regulating water and solute permeability, and modulating signaling pathways involved in cell differentiation and proliferation. Their extracellular loops serve as receptors for bacterial adhesins, notably the FimH lectin of uropathogenic Escherichia coli, facilitating attachment during urinary tract infections.

Mutations or altered expression of uroplakin genes have been linked to congenital abnormalities such as vesicoureteral reflux, bladder outlet obstruction, and certain forms of interstitial cystitis. Additionally, uroplakins are investigated as biomarkers for urothelial carcinoma, with loss of UPK expression often correlating with higher grade malignancies.

Research continues to explore uroplakin‑based therapeutics, including vaccine candidates targeting the bacterial binding domains and engineered urothelial tissue models for drug testing and regenerative medicine.