Sperm-associated antigen 6 (SPAG6): roles in human cancer and other diseases

Emerging evidence indicates that sperm-associated antigen 6 (SPAG6), a protein initially characterized for its role in ciliogenesis and spermatogenesis, plays critical roles not only in the genital system but also in the nervous, immune, and hematopoietic systems. More recently, SPAG6 has been increasingly implicated in cancer progression and treatment. In this review, we systematically summarize the molecular characterization of SPAG6 and delineate its functional roles and pathophysiological mechanisms across multiple organ systems. We also review its therapeutic relevance in cancer management, especially in hematopoietic malignancy. Notably, SPAG6 was found to be aberrantly overexpressed in clinical myelodysplastic syndrome (MDS) patients and promote the proliferation of MDS-L cells. While functional discrepancies of SPAG6 across experimental models warrant further in-depth exploration, elucidating its mechanisms in disease pathogenesis could offer valuable insights for developing targeted therapies for human diseases.