PKP3 (plakophilin 3) is a desmosomal plaque protein primarily functioning in cell-cell adhesion and epithelial barrier maintenance. As a core desmosomal component, PKP3 binds desmogleins, desmocollins, plakoglobin, and desmoplakin to facilitate desmosome assembly and stability 1. PKP3 regulates localization of desmosomal proteins (DSG2, DSP, PKP2) to mature junctions and stabilizes PKP2 mRNA through FXR1 interaction, supporting structural integrity of epithelial tissues 1. Beyond adhesion, PKP3 exhibits oncogenic properties in multiple cancers. In lung adenocarcinoma, the circIGF2BP3/PKP3 axis promotes immune escape by stabilizing PD-L1 through OTUB1-mediated deubiquitination, suppressing CD8+ T cell infiltration 2. In pancreatic cancer, PKP3 drives acinar-to-ductal metaplasia and promotes progression by stabilizing FOXM1, with nuclear localization correlating with malignancy 3. PKP3 loss paradoxically increases autophagy and radioresistance in some contexts 4, while elevated PKP3 promotes ovarian cancer proliferation, invasion, and metastasis via MAPK-mTOR pathway activation 5. Clinically, PKP3 dysregulation occurs across breast, ovarian, colon, and lung cancers, with elevated expression predicting poor prognosis in PDAC 6. Loss of PKP3 causes skin diseases including paraneoplastic pemphigus and pemphigus vulgaris 6. Thus PKP3 functions dually as a structural adhesion protein and cancer-promoting oncogene.