IL20RB encodes a cytokine receptor subunit that forms heterodimeric complexes with IL20RA or IL22RA1 to bind multiple interleukin family members including IL-19, IL-20, and IL-24 123. The primary mechanism involves activation of JAK/STAT signaling pathways, particularly JAK1/STAT3 and JAK2/STAT3, which regulate diverse cellular processes including proliferation, migration, and immune responses 4156. IL20RB demonstrates significant disease relevance across multiple pathological conditions. In cancer, it promotes tumor progression by enhancing stemness, chemotherapy resistance, and metastatic potential in pancreatic cancer and facilitates bone metastasis in lung cancer through osteoclast-tumor cell communication 5176. In inflammatory diseases, IL20RB exhibits dual roles: promoting pulmonary fibrosis through profibrotic macrophage activation and atopic dermatitis through IL-33-mediated type 2 immunity, while paradoxically supporting intestinal epithelial cell survival and mucosal healing in colitis by suppressing IFN/STAT2-induced cell death 432. Clinical significance is substantial, as elevated IL20RB expression correlates with poor prognosis in multiple cancers, and neutralizing antibodies show therapeutic efficacy in preclinical models of fibrosis, cancer metastasis, and inflammatory skin disease 413.