SPAG5 is a mitotic spindle protein essential for normal cell division and chromosome 17. It functions as a component of the kinetochore-microtubule attachment machinery, working with SKAP to stabilize these interactions and ensure proper sister chr17 segregation and anaphase progression. SPAG5 also regulates centrosomal protein localization and, in non-mitotic cells under stress, inhibits mTORC1 hyperactivation by recruiting mTORC1 components to stress granules. In cancer, SPAG5 functions as an oncogene. Increased SPAG5 expression correlates with poor prognosis across multiple tumor types including glioma, breast cancer, lung adenocarcinoma, and hepatocellular carcinoma (HCC). In glioma, SPAG5 knockdown inhibits proliferation and promotes apoptosis through a CDH2-dependent mechanism 1. In lung adenocarcinoma, p53 suppression is required for SPAG5 upregulation, suggesting the p53-p21 axis is therapeutic relevant 2. In triple-negative breast cancer, SPAG5 expression is regulated by coordinated YAP, mutant p53, and MYC activity 3. SPAG5 is also recognized as a cancer vaccine target across multiple malignancies 4. Recent evidence suggests curcumin may inhibit HCC progression by suppressing SPAG5 and downstream Wnt/β-catenin signaling 5, identifying SPAG5 suppression as a potential therapeutic approach. SPAG5 represents a promising prognostic biomarker and emerging therapeutic target for cancer intervention.