Tnfrsf10b, also known as TRAIL-R2 or DR5, codes for a pro-apoptotic receptor activated by TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) and is involved in apoptosis-related pathways, playing a crucial role in immune surveillance against virus-infected or transformed cells [1,7].

In chronic lymphocytic leukemia (CLL), del(8p) is associated with poor prognosis and fludarabine resistance, and TNFRSF10B is haploinsufficient in 91% of del(8p) CLL cases, involved in modulating fludarabine-induced cell death [1].

In non-small cell lung cancer, certain TNFRSF10B polymorphisms and haplotypes are associated with an increased risk of death [2].

In diabetic kidney disease, TNFRSF10B expression is increased in podocytes, and TRAIL/DR5 signaling via TNFRSF10B promotes podocyte PANoptosis, with podocyte-specific deletion of TNFRSF10B alleviating podocyte and glomerular injury in diabetic mice [3].

In non-small cell lung cancer cells, YIPF2 promotes chemotherapeutic agent-mediated apoptosis by enhancing TNFRSF10B recycling to the plasma membrane [4].

In lung adenocarcinoma, TNFRSF10B mRNA is preferentially expressed in EGFR wild-type tumors, and strong TRAIL-R2 (encoded by TNFRSF10B) expression predicts a poor prognosis [5].

In HPV-positive head and neck squamous cell carcinomas, combining a death agonist antibody against TNFRSF10B with birinapant enhances anti-tumor activity [6].

Hepatitis B virus-triggered autophagy targets TNFRSF10B for degradation, limiting the TNFSF10/TRAIL response, allowing virus-infected cell survival [7].

In conclusion, Tnfrsf10b is essential for apoptosis-related biological processes. Studies using gene-knockout or cell-specific knockout models in various diseases such as leukemia, lung cancer, and diabetic kidney disease have revealed its role in disease prognosis, response to treatment, and disease-related cellular processes. Understanding Tnfrsf10b's functions through these models provides insights into disease mechanisms and potential therapeutic targets.