TNFSF10 (TNF superfamily member 10), also known as TRAIL (TNF-related apoptosis-inducing ligand), is a cytokine that binds to death receptors TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, and other TRAIL receptors to induce apoptosis 12. The protein functions through extrinsic apoptotic signaling, triggering caspase reactions and cytochrome c release from mitochondria, with activity modulated by decoy receptors that prevent apoptotic signaling 3. TNFSF10 expression is regulated by pro-inflammatory cytokines and shows autocrine signaling properties on immune cells 4. In disease contexts, TNFSF10 upregulation contributes to pathology: elevated TRAIL/DR5 expression in diabetic kidney disease podocytes promotes PANoptosis (combined apoptosis, pyroptosis, and necroptosis), with podocyte-specific TNFSF10 deletion alleviating kidney injury in diabetic mice 5. Similarly, TNFSF10 downregulation in dry eye disease mitigates NLRP3-mediated pyroptosis in corneal epithelial cells 6. Therapeutically, aponermin, a recombinant TRAIL variant, received first approval in China for relapsed/refractory multiple myeloma by activating death receptors 4 and 5 on tumor cells 3. Additionally, TNFSF10 genetic variants predict radiosensitivity in lymphocytes and radiation-induced dermatitis, suggesting biomarker potential for personalized radiotherapy 4.