In summary, the specificity of receptor selection is helpful to (i) investigate specific signaling pathways, such as D143N-A145R was used to study the TNFR2-specific signaling pathway, (ii) reduce side effects, such as TNFR1-specific ligand R32W-S86T, which was found to be lethal to tumor cells with low proinflammatory effects, and (iii) increase efficacy of ligands, such asDR5-specific ligand DHER, which induced more cancer cell death than TRAIL WT by escaping from the neutralization of the decoy receptor OPG. The gene discussed is TNFRSF1B; the disease is neoplasm.