GADD34-mediated dephosphorylation of eIF2α inhibits the unfolded protein response (UPR). The study identifies GADD34 as a gene that suppresses the UPR by dephosphorylating eIF2α, thereby reducing stress-induced gene expression. GADD34 forms a complex with the catalytic subunit of protein phosphatase 1 (PP1c), promoting eIF2α dephosphorylation. This process is essential for negative feedback regulation of the UPR, which helps cells recover from translational inhibition. GADD34 expression is stress-dependent and is absent in PERK- and GCN2-deficient cells. The study shows that GADD34 inhibits the activation of CHOP and BiP, two key genes in the UPR. The findings suggest that GADD34-mediated dephosphorylation of eIF2α is part of a negative feedback loop that attenuates signaling in the integrated stress response. The results highlight the role of GADD34 in regulating eIF2α phosphorylation and its importance in the UPR. The study also demonstrates that GADD34 interacts with PP1c and that its activity is dependent on this interaction. The findings provide insights into the mechanisms of stress response regulation and the role of GADD34 in maintaining cellular homeostasis.GADD34-mediated dephosphorylation of eIF2α inhibits the unfolded protein response (UPR). The study identifies GADD34 as a gene that suppresses the UPR by dephosphorylating eIF2α, thereby reducing stress-induced gene expression. GADD34 forms a complex with the catalytic subunit of protein phosphatase 1 (PP1c), promoting eIF2α dephosphorylation. This process is essential for negative feedback regulation of the UPR, which helps cells recover from translational inhibition. GADD34 expression is stress-dependent and is absent in PERK- and GCN2-deficient cells. The study shows that GADD34 inhibits the activation of CHOP and BiP, two key genes in the UPR. The findings suggest that GADD34-mediated dephosphorylation of eIF2α is part of a negative feedback loop that attenuates signaling in the integrated stress response. The results highlight the role of GADD34 in regulating eIF2α phosphorylation and its importance in the UPR. The study also demonstrates that GADD34 interacts with PP1c and that its activity is dependent on this interaction. The findings provide insights into the mechanisms of stress response regulation and the role of GADD34 in maintaining cellular homeostasis.