Unfolded protein response（UPR） is a protective response in cell endoplasmic reticulum （ER） under stress condition. Three ER transmembrane proteins, IRE1, PERK, and ATF6, coordinately regulate the UPR function in mammalian cells through their signaling pathways. In addition, some proteins and transcription factors during the UPR can provide negative and positive feedback loops to maintain the normal function of ER. UPR can trigger cell death or apoptosis and eventually cause related diseases if the ER stress persists. Several key mediators of UPR are candidates for therapeutic targets in many studies. Up to now progress has been made in the area, which provides new ideas for clinical practice and holds a great potential for future application.[