GADD45G (growth arrest and DNA damage inducible gamma) is a stress-responsive protein that functions as a critical regulator of cellular stress responses and disease pathogenesis. Structurally, GADD45G operates as a small, ubiquitously distributed protein 1 that localizes to both cytoplasm and nucleus where it mediates activation of the MAP kinase cascade, particularly through MTK1/MEKK4 and MAP3K4 signaling 2. Mechanistically, GADD45G regulates cell cycle arrest, DNA repair, and apoptosis through NF-κB and interferon regulatory factor 3 (IRF3) pathways 2. Beyond DNA damage responses, GADD45G functions as a pathological sensor orchestrating reactive gliosis in neuroinflammation 2. Clinically, GADD45G dysregulation is implicated in multiple diseases: its reduction in myeloproliferative neoplasms promotes hematopoietic stem cell expansion through RAC2/PAK1/PI3K-AKT signaling 3, while elevated expression in astrocytes aggravates Alzheimer's disease pathology through neuroimmune activation 2. GADD45G emerges as a shared biomarker linking non-alcoholic fatty liver disease and Alzheimer's disease 4. Additionally, GADD45G mediates inflammatory responses in intervertebral disc degeneration 5 and genotoxicity in corneal epithelial cells 6, positioning it as a promising therapeutic target across multiple pathological conditions.