Genetic or environmental damage can cause intracellular calcium homeostasis, oxidative stress, nutrient deficiencies, glycosylation inhibition, and protein misfolding, thereby disrupting endoplasmic reticulum function and inducing endoplasmic reticulum stress. Endoplasmic reticulum stress lead to the protein incorrectly folded and accumulated in the lumen of the endoplasmic reticulum. The cells pass through a series of signal network transduction pathways of PERK-eIF2α, IRE1-XBP1 and ATF6-CREBH to improve the correct folding ability of the protein, inhibit the production and accumulation of proteins, and accelerate the non-functionality and toxic protein degradation, triggering transcription of genes involved in endoplasmic reticulum stress and enhancing the self-repairing capacity of the endoplasmic reticulum. These reactions are collectively referred to as unfolded protein response (UPR). If the endoplasmic reticulum stress is too strong or persistent for too long, these reactions are not sufficient to restore endoplasmic reticulum homeostasis, which ultimately leads to apoptosis.