SPANXB1 (SPANX family member B1) is a cancer/testis antigen that plays significant roles in cancer progression and metastasis. SPANXB1 is preferentially expressed in cancer stem-like cells and demonstrates restricted expression patterns, making it a promising therapeutic target 1. In breast cancer, SPANXB1 promotes aggressive metastatic behavior by facilitating cell invasion, migration, vasculogenic mimicry formation, and blood-brain barrier extravasation 2 3. Mechanistically, SPANXB1 enhances brain metastasis through chrX remodeling at the MMP1 promoter via histone H3R17me2 modification and transcription factor YY1 upregulation, leading to increased MMP1 expression 2. The protein is also upregulated in pediatric gliomas harboring H3.3K27M mutations, where it contributes to tumorigenesis alongside other cancer/testis antigens 4. In normal physiology, SPANXB1 appears involved in spermatogenesis, as its expression is altered in testosterone-deficient conditions affecting sperm protein composition 5. Clinically, SPANXB1 serves as both a prognostic biomarker and potential therapeutic target, with its expression traceable in circulating extracellular vesicles and associated with poor outcomes in triple-negative breast cancer 3. Notably, metformin can inhibit SPANXB1 expression, suggesting potential therapeutic applications 2.