PKP1 (plakophilin 1) is a desmosomal plaque protein that functions primarily in cell-cell adhesion and cellular integrity. At the molecular level, PKP1 localizes to desmosomes at the cell membrane-cytoplasm interface and regulates desmosome protein expression, localization, and anchorage to intermediate filaments 1. PKP1 is required for DSG3 and YAP1 localization to cell membranes in keratinocytes under mechanical strain 2 and positively regulates keratinocyte differentiation and proliferation during development 3. Beyond adhesion functions, PKP1 promotes cap-dependent translation by recruiting EIF4A1 to translation initiation complexes 41 and regulates mRNA stability of desmosomal components through interaction with FXR1 5. Loss-of-function PKP1 mutations cause ectodermal dysplasia-skin fragility syndrome (EDSF), characterized by skin erosions, palmoplantar hyperkeratosis, and ectodermal abnormalities 6. Notably, PKP1 exhibits contradictory roles in cancer: while downregulated in prostate cancer (suggesting tumor-suppressive functions) 7, it is recurrently overexpressed in squamous cell lung cancer where it enhances MYC translation through a feedforward loop with MYC transcription 8. In esophageal squamous carcinoma, a PKP1-containing prognostic signature correlates with patient survival and drug sensitivity 9. PKP1's role in breast cancer involves lncRNA APPAT-mediated regulation via the miR-328a/PKP1 pathway 10.