EPPK1 (epiplakin 1) is a cytoskeletal linker protein that connects intermediate filaments and controls their reorganization in response to stress 123. In normal physiology, EPPK1 plays a dual role in epithelial tissues: it slows keratinocyte migration while accelerating keratin bundling to maintain tissue architecture 23, and regulates intermediate filament organization by reducing traction forces and affecting cellular morphology 4. Clinically, EPPK1 dysfunction is implicated in multiple cancers through oncogenic pathways. In bladder cancer, dihydrotestosterone promotes cell proliferation and invasion via EPPK1-mediated MAPK/JUP signaling 5. In lung adenocarcinoma and esophageal squamous cell carcinoma, EPPK1 overexpression correlates with poor prognosis and drives cancer progression through PI3K-AKT pathway activation and epithelial-to-mesenchymal transition 67. Similarly, in cervical cancer, KLF5-mediated EPPK1 expression promotes proliferation via p38 signaling 8. EPPK1 mutations associate with colorectal cancer development linked to mismatch repair deficiency 9, and EPPK1 is identified as a potential driver gene in intrahepatic cholangiocarcinoma 10. Conversely, EPPK1 downregulation occurs in psoriatic skin, where interferon-γ-dependent reduction correlates with barrier dysfunction and epithelial defects 11, suggesting context-dependent roles in disease pathology.