Uroplakin

Uroplakin, or uroplakins, refers to a family of membrane proteins expressed predominantly in the urothelium of the urinary tract. They are major components of the asymmetric unit membrane plaques that cover the apical surface of umbrella cells and contribute to the bladder’s permeability barrier, helping to protect underlying tissues from urine solutes and microorganisms.

The uroplakin family comprises several members, including UPK1A, UPK1B, UPK2, UPK3A, and UPK3B. UPK1A forms a heterodimer with UPK2, while UPK1B forms heterodimers with UPK3A or UPK3B. These heterodimers assemble into 16-nm urothelial plaques that organize into two-dimensional crystalline arrays on the apical membrane of umbrella cells. The proteins are glycosylated transmembrane proteins that contribute to the mechanical strength and barrier function of the urothelium.

Expression of uroplakins is tied to urothelial differentiation; they are abundant in the differentiated umbrella cell layer and serve as markers of urothelial lineage in histology. Their presence supports the formation and maintenance of the urothelial barrier, and they may be involved in membrane trafficking and turnover associated with the apical surface.

Clinical and research significance: uroplakins are used as immunohistochemical markers to identify urothelial origin in pathological samples. In urothelial carcinomas, UPK expression is typically assessed to help confirm urothelial differentiation, with loss or alteration of expression associated with higher-grade tumors in some cases. Beyond cancer, uroplakins are studied to understand bladder biology and barrier function.