SDC1 (syndecan-1) is a cell surface heparan sulfate and chondroitin sulfate proteoglycan that functions as a critical mediator of cell-matrix interactions and multiple oncogenic processes. Mechanistically, SDC1 regulates exosome biogenesis in concert with SDCBP and PDCD6IP 1. In cancer contexts, SDC1 operates through diverse pathways: it mediates macropinocytosis in pancreatic cancer downstream of KRAS signaling 2, facilitates tumor-immune crosstalk via CCL5 receptor-ligand interactions in pancreatic cancer 3, and coordinates autophagosome-lysosome fusion through the SDC1-TGM2-FLOT1-BHMT complex to enhance glioblastoma radioresistance 4. In cervical cancer, soluble SDC1 shed from cancer-associated fibroblasts promotes tumor cell proliferation and migration via the MDK-SDC1 signaling axis 5. SDC1 expression patterns are cancer-type dependent: reduced expression correlates with advanced stages in gastric and colorectal cancers, while overexpression promotes growth in pancreatic and breast cancers 6. In breast cancer, SDC1 disturbs tumor stem cell phenotypes and modulates macrophage migration and epithelial-mesenchymal transformation 7. In liver disease, elevated SDC1 expression characterizes cirrhosis and hepatocellular carcinoma, with serum levels of cleaved SDC1 reflecting poor prognosis 8. These findings position SDC1 as a multi-functional oncogenic proteoglycan with potential as a therapeutic target across multiple cancer types.