Abstract: Ischemia-reperfusion injury (IRI) and rejection are the main factors affecting the long-term survival of transplant kidneys. IRI or rejection reactions can cause endoplasmic reticulum stress (ERS) leading to renal injury. X-box binding protein 1 (XBP1), as the main ERS-related protein regulating cell homeostasis, generates spliced XBP1 after splicing introns by inositol-requiring enzyme 1α (IRE1α), thereby affecting the expression of target genes and reshaping the cell environment. Appropriate ERS can promote cell survival. However, when the threshold is exceeded, excessive expression of XBP1 can lead to cell instability or death, thereby causing an imbalance in the renal internal environment, which is related to the pathogenesis and progression of kidney transplant-related injury. Therefore, the effective activation of XBP1 has a protective effect on stress injury and helps maintain the vitality and integrity of the renal system. This article reviews the ERS pathway IRE1α-XBP1, the role of XBP1 in renal parenchymal cells and immune cells, the role of XBP1 in renal ischemic injury and rejection, and the clinical detection and potential therapies targeting XBP1. It explores the potential value of targeting XBP1 in kidney transplant-related injury, aiming to provide new targets and directions for improving the prognosis of kidney transplantation.