Introduction:The glycoprotein clusterin (CLU) plays a pivotal role in vital cellular functions, including cell proliferation and DNA damage repair. Its frequent overexpression in tumor cells, particularly in gliomas, positions it as a promising therapeutic target. This study aims to investigate the impact of CLU dysregulation on glioma cell lines and explore its therapeutic potential. Methods:Two human astrocytic cell lines, CCF-STTG1 astrocytoma cells, and SV-40 immortalized normal human astrocytes, were utilized in our investigation. CLU expression was suppressed using transient siRNA transfection, and subsequent effects on cell proliferation, DNA damage response, and cell cycle progression were meticulously evaluated. Results: Silencing CLU expression significantly impeded cell proliferation and induced the DNA damage response in both glioma cell lines. Moreover, cell cycle arrest was observed following CLU silencing, suggesting its regulatory role in cell cycle progression. Conclusion: These findings underscore the therapeutic potential of targeting CLU in gliomas, providing a novel approach to inhibit glioma cell growth and improve patient prognosis. The study also highlights the multifaceted role of CLU in regulating various cellular processes, including growth factor signaling, apoptosis regulation, and DNA damage response. Dysregulation of CLU expression or activity may contribute to aberrant cell proliferation observed in various diseases, emphasizing the importance of exploring CLU as a therapeutic target in gliomas.