Junction plakoglobin (JUP) is a multifunctional cell adhesion molecule that serves as a critical component of desmosomal and adherens junctions, where it functions as a common junctional plaque protein linking cadherins to the cytoskeleton. JUP can substitute for β-catenin in E-cadherin/catenin complexes, coupling cadherins to actin and thereby maintaining cell-cell adhesion architecture 1. Beyond its canonical adhesive role, JUP participates in diverse signaling pathways including Wnt/β-catenin and p53-mediated signaling, demonstrating context-dependent functions in cellular regulation 1. Clinically, JUP mutations cause hereditary arrhythmogenic right ventricular dysplasia and Naxos disease, highlighting its importance in cardiac tissue integrity and intercalated disc function. In cancer biology, JUP exhibits dual roles: it can suppress tumorigenesis through adhesive functions, yet its degradation via the XAF1-VCP-RNF114-JUP axis promotes colorectal cancer metastasis by facilitating cell migration 2. This degradation-dependent promotion of metastasis suggests that loss of JUP-mediated cell-cell adhesion provides a selective advantage for invasive cancer cells 2. JUP's emerging roles across multiple cancer types underscore its potential as a diagnostic, prognostic, and therapeutic target in malignant disease 1.