TNFRSF10D (TRAIL-R4) functions as a decoy receptor for the cytotoxic ligand TRAIL, containing a truncated death domain that prevents apoptosis induction while protecting cells against TRAIL-mediated cell death 1. The protein exhibits contradictory reports regarding its ability to activate the NF-κB pathway, with some studies supporting activation while others do not 23. Expression analysis reveals TNFRSF10D is differentially expressed in osteosarcoma cells compared to normal cells, with abundant expression in endothelial cells and osteoblastic cells 4. In cancer contexts, TNFRSF10D upregulation correlates with treatment responses and resistance mechanisms. Cisplatin treatment dramatically increases TNFRSF10D expression (~100-fold) in cisplatin-resistant ovarian cancer cells, potentially promoting cell survival through non-canonical NF-κB pathway activation 5. The gene is frequently silenced by DNA methylation in melanoma, and its methylation status serves as a significant prognostic biomarker for both overall and relapse-free survival 67. Additionally, TNFRSF10D expression increases following quercetin treatment in gastric cancer cells as part of apoptotic pathways 8, and its interactions are altered in immune checkpoint inhibitor therapy responses 9.