COPG1 encodes coat protein complex I subunit gamma 1, a component of the coatomer complex essential for vesicular transport within the early secretory pathway. COPG1 functions as part of COPI, which mediates retrograde transport from the Golgi to the endoplasmic reticulum and intra-Golgi trafficking 1. The protein binds to dilysine motifs on transport vesicles and requires ARF-GTP for membrane recruitment, facilitating protein secretion and maintaining Golgi structural integrity [UniProt summary]. Deficiency in COPG1 disrupts multiple cellular processes with significant disease implications. Loss of COPG1 or other COPI subunits aberrantly activates STING signaling and type I interferon responses through impaired retrograde transport, a mechanism also implicated in immunodeficiency syndromes 1. COPG1 mutations have been identified in malignant mesothelioma and associated with asbestos-exposed tumors 2. In dengue virus infection, COPG1 is required for efficient secretion of viral non-structural protein 1, indicating exploitation of COPI machinery by pathogens 3. Clinically, COPG1 emerges as an oncogenic driver and therapeutic target. Pan-cancer analysis reveals COPG1 upregulation correlates with poor prognosis (HR > 2) across multiple cancers, with particular significance in hepatocellular carcinoma 4. COPG1 depletion induces Golgi disruption, increases reactive oxygen species, and suppresses PI3K-AKT signaling, sensitizing cancer cells to chemotherapy 4. Genome-wide association studies identified COPG1 as associated with increased breast cancer risk 5.