SRGN (serglycin) is a proteoglycan that plays critical roles in cancer progression through multiple mechanisms. In cancer cells, SRGN functions as an oncogenic factor promoting tumor aggressiveness and metastasis. In glioblastoma, SRGN specifically maintains stemness and proliferation of mesenchymal glioblastoma stem cells through the SRGN-NFκB axis while mediating resistance to macrophage phagocytosis 1. In lung adenocarcinoma, SRGN is markedly overexpressed in TTF-1-negative tumors and regulates PD-L1 expression and proinflammatory cytokines, creating an immunosuppressive tumor microenvironment associated with poor prognosis 2. SRGN promotes hepatocellular carcinoma aggressiveness by activating the YAP/CRISPLD2 axis, enhancing stemness-like characteristics and metastatic behavior 3. In the tumor microenvironment, SRGN secreted by cancer cells activates cancer-associated fibroblasts through the CD44/c-Myc pathway to promote IL-8 production in gastric cancer 4. Under hypoxic conditions, SRGN is released via secretory autophagy and interacts with MMP2/9 to enhance extracellular matrix remodeling and invasion in oral squamous cell carcinoma 5. SRGN also contributes to chemoresistance in breast cancer, where its downregulation by miR-26b-5p can restore drug sensitivity 6. Additionally, SRGN is involved in adipose tissue inflammation during obesity 7.