SPAG6 (sperm associated antigen 6) is a microtubule-binding protein that serves as the mammalian orthologue of Chlamydomonas PF16, primarily functioning in flagellar motility and axonemal structure 1. The protein localizes to sperm tails and contains eight armadillo repeats that mediate protein-protein interactions, placing it in the central pair apparatus of the flagellar axoneme 1. SPAG6 expression is highly enriched in testis, with the gene mapping to chromosome 10.2-p12 1. Functionally, SPAG6 serves as a central pair marker, as evidenced by its reduced abundance in sperm with flagellar axoneme defects, including central pair microtubule deficiency 2. Beyond reproductive function, SPAG6 has emerged as clinically significant in cancer biology. Overexpression of SPAG6 correlates with poor prognosis in osteosarcoma, showing positive associations with pathological grade, metastasis, and Enneking stage 3. In breast cancer, SPAG6 promotes tumor progression through the PI3K/Akt pathway, with circMYH9 enhancing SPAG6 mRNA stability by recruiting EIF4A3 4. Additionally, SPAG6 methylation patterns serve as potential liquid biopsy biomarkers for triple-negative breast cancer detection 5. The protein functions in various physiological processes including ciliary movement, immune synapse formation, and represents a potential therapeutic target in multiple malignancies 6.