Mechanistically, our experiments indicated that DcR2 specifically interacts with GRP78, enhances GRP78–caspase 7 interactions, and disturbs the balance between anti- and proapoptotic protein expression, ultimately leading to apoptosis resistance, accumulation of senescent cells, sustained SASP secretion, and renal fibrosis. The gene discussed is TNFRSF10D; the disease is renal fibrosis.