PPP1R15A encodes GADD34 (Growth Arrest and DNA Damage-inducible protein 34), a regulatory subunit of protein phosphatase 1 that plays a central role in the integrated stress response (ISR). The primary function involves dephosphorylating eIF2α to restore protein synthesis following cellular stress 1. Mechanistically, PPP1R15A binds P-eIF2 in complex with eIF2B and enables dephosphorylation of otherwise dephosphorylation-incompetent P-eIF2, thereby rescuing eIF2B from inhibition and terminating the ISR 1. The gene is tightly regulated post-transcriptionally through AU-rich elements in its 3' UTR that control mRNA stability, with rapid decay under normal conditions and stabilization during stress 2. Disease relevance includes promoting gastric cancer progression by activating autophagy under energy stress conditions 3, contributing to immunosuppression in hepatocellular carcinoma through monocytic myeloid-derived suppressor cells 4, and genetic variants associated with cancer susceptibility 5. Clinically, PPP1R15A represents a potential therapeutic target, with pharmacological inhibition showing promise in reducing immunosuppressive activity in cancer models 4. Additionally, PPP1R15A deficiency can lead to severe cardiac dysfunction and cachexia through GDF15-mediated pathways 6.