SEC61G (SEC61 translocon subunit gamma) is a component of the SEC61 translocon complex mediating protein translocation across the endoplasmic reticulum membrane and ER insertion of transmembrane proteins. Beyond its canonical role in protein import, SEC61G has emerged as a critical oncogenic factor across multiple cancer types. In non-small cell lung cancer, SEC61G drives brain metastasis by stabilizing the glycolytic enzyme PGAM1 through competitive inhibition of UBE3C-mediated ubiquitination, while simultaneously promoting immune evasion via M2 microglia polarization 1. In kidney cancer, SEC61G upregulation promotes tumor progression by enhancing cell proliferation, migration, and invasion while suppressing apoptosis through epithelial-mesenchymal transition pathways 2. SEC61G overexpression correlates with poor prognosis in head and neck squamous cell carcinoma, independent of DNA amplification status, and negatively correlates with infiltration of anti-tumor immune cells 3. In colorectal cancer, SEC61G promotes progression by increasing cytosolic calcium levels, which activate EGFR signaling and cell cycle progression 4. Similarly, in breast cancer, SEC61G enhances glycolysis and is transcriptionally regulated by E2F1, promoting tumorigenesis and metastasis 5. Additionally, SEC61G shows differential methylation in Balkan endemic nephropathy patients 6 and altered expression in Alzheimer's disease immune microenvironments 7. These findings position SEC61G as a promising prognostic biomarker and therapeutic target.