Uroplakin 2 (UPK2)

Uroplakin 2 (UPK2) is an integral membrane glycoprotein, crucial for the formation of apical urothelial plaques that line the urinary tract (bladder, ureters, renal pelvis, and parts of the urethra). It plays a vital role in maintaining the permeability barrier of the urothelium, preventing toxic urinary substances from entering deeper tissues, and ensuring structural integrity during bladder distension. UPK2 is synthesized in the endoplasmic reticulum, dimerizes with Uroplakin Ia, and then assembles into the 16 nm hexagonal plaques in the Golgi, forming part of a tetramer complex including UPK1b and UPK3a. This structural protein is essential for urothelial differentiation. It is highly specific for urothelial cells and serves as a standard immunohistochemical marker for confirming the urothelial origin of tumors, especially in urothelial carcinoma, improving diagnostic sensitivity in tissue and sometimes in blood/urine. While not a classic pharmacological target or a signal transducer/enzyme, UPK2 is functionally relevant in urogenital development, urinary tract infection susceptibility (as uroplakins are essential for uropathogenic E. coli attachment), and cancer pathology. Genetic deletion of UPK2 leads to severe urothelial defects, urine leakage, and early lethality in animal models, underscoring its indispensable physiological function. Its canonical gene symbol is UPK2 (UniProt O00526), and it features a single transmembrane domain, forming heterodimers and multiprotein complexes in the asymmetric unit membrane. Although not a target for therapeutic drugs, UPK2 antibodies are widely used for diagnostic identification and classification of urothelial carcinomas.

Other names

UPK2UPIIuroplakin II

Not directly targeted by known drugs; instead, largely a biomarker for urothelial origin and differentiation, as well as a host structure facilitating pathogen (e.g., UPEC) adhesion.