Functionally, TTC23 depletion suppressed migratory capacity, increased apoptotic susceptibility, reduced short-term viability, and impaired long-term clonogenic survival, while sensitizing GBM cells to CPZ-associated anti-tumor phenotypes.<h4>Conclusion</h4>Our multi-layer framework nominates TTC23 as a functionally relevant determinant associated with CPZ response in GBM and supports the CPZ-TTC23 axis as a candidate for biomarker-informed drug repurposing. Here, CPZ is linked to glioblastoma.