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Classical pathway for maintaining ER homeostasis. Unfolded proteins activate UPR sensors IRE1α, PERK, and ATF6, which regulate UPR-associated target genes and maintain ER homeostasis. XBP1-s regulates ERAD and alleviates ER stress. IRE1α: inositol-requiring protein 1α; PERK: PERK-like ER kinase; ATF6: activating transcription factor 6; ERAD: ER-associated protein degradation.
