TNFRSF19 (TNF receptor superfamily member 19) is a transmembrane receptor that functions as a key regulator of cell differentiation, proliferation, and immune signaling. As a TNF receptor superfamily member, TNFRSF19 mediates activation of JNK and NF-κB signaling pathways and can promote caspase-independent cell death through transmembrane signaling mechanisms. Mechanistically, TNFRSF19 acts as a downstream target of canonical Wnt/β-catenin signaling 1. In mesenchymal stem cells, TNFRSF19 promotes osteoblastic differentiation while inhibiting adipogenesis through C/EBP-mediated regulation 1. In hepatocellular carcinoma, TNFRSF19 downregulation—mediated by the oncogenic miRNA miR-HCC3—drives proliferation and epithelial-mesenchymal transition, suggesting a tumor-suppressive role 2. Clinically, TNFRSF19 shows significant disease relevance across multiple contexts. In NAFLD-associated HCC, mutant β-catenin upregulates TNFRSF19, which then suppresses senescence-associated secretory cytokines (IL6, CXCL8) to promote immune evasion 3. A TNFRSF19-containing signature in colorectal cancer stem cells correlates with patient prognosis 4. In prostate cancer, TNFRSF19 expression within cancer-associated fibroblasts predicts superior survival outcomes and represents an immune-related biomarker 5. These findings establish TNFRSF19 as a multifunctional regulator with context-dependent roles in differentiation, immune regulation, and cancer biology.