CENPS (centromere protein S) is a histone fold protein that functions as a component of the constitutive centromere-associated network (CCAN), a complex of 16 proteins essential for kinetochore assembly and chromosome 1 1. CENPS works in conjunction with related proteins like CENPX (also known as MHF1/2) to facilitate centromeric chr1 organization and mitotic progression 2. Beyond its canonical centromeric role, CENPS participates in DNA damage response (DDR) mechanisms. Upon DNA double-strand breaks, CENPS is rapidly recruited to damage sites with a half-life of approximately 100 seconds, positioning it during early chr1 remodeling and nucleosome reorganization phases 3. This recruitment occurs simultaneously with ATM activation and precedes RAD51 loading, suggesting involvement in pathway choice and DNA resection during homologous recombination 3. Clinically, CENPS expression is significantly elevated in multiple cancer types. In hepatocellular carcinoma, CENPS upregulation correlates with poor prognosis and promotes cancer progression through transcriptional cooperation with YY1 to activate oncogenic genes 4. Similarly, elevated CENPS expression in ovarian cancer is associated with worse prognosis and relates to immune infiltration patterns 5. These findings suggest CENPS dysregulation contributes to cancer development through both mitotic and transcriptional mechanisms, making it a potential therapeutic target.