SPARC (secreted protein acidic and cysteine rich) is a matricellular protein that functions as a critical regulator of cellular behavior, inflammation, and extracellular matrix homeostasis 1. The protein contains calcium-binding domains and mediates collagen deposition and assembly in tissues, with SPARC-deficient mice showing reduced fibrillar collagen in multiple organs 2. SPARC operates through diverse mechanisms including modulation of immune responses, where it converts anti-inflammatory macrophages to a pro-inflammatory phenotype via TLR4-mediated TBK1, IRF3, IFN-β, and STAT1 signaling pathways 1. In cancer contexts, SPARC demonstrates complex roles: it stabilizes ApoE protein to promote cholesterol accumulation and invasion in hepatocellular carcinoma while conferring sorafenib resistance 3, and is upregulated in colorectal cancer liver metastases where it correlates with stem cell markers and enhanced malignancy 4. Conversely, SPARC functions as an anti-cancer myokine that increases following exercise and suppresses breast cancer cell growth in vitro 5. The protein also participates in gastric cancer regulation, where LCN2 suppresses SPARC expression through the 24p3R/JNK/c-Jun pathway, linking SPARC to tumor progression 6. Clinically, SPARC mutations cause osteogenesis imperfecta, highlighting its essential role in bone metabolism and collagen biology.