{Reference Type}: Journal Article {Title}: Exploring Ubiquitin-specific proteases as therapeutic targets in Glioblastoma. {Author}: Samuel VP;Moglad E;Afzal M;Kazmi I;Alzarea SI;Ali H;Almujri SS;Abida ;Imran M;Gupta G;Chinni SV;Tiwari A; {Journal}: Pathol Res Pract {Volume}: 260 {Issue}: 0 {Year}: 2024 Aug 1 {Factor}: 3.309 {DOI}: 10.1016/j.prp.2024.155443 {Abstract}: Glioblastoma (GB) remains a formidable challenge and requires new treatment strategies. The vital part of the Ubiquitin-proteasome system (UPS) in cellular regulation has positioned it as a potentially crucial target in GB treatment, given its dysregulation oncolines. The Ubiquitin-specific proteases (USPs) in the UPS system were considered due to the garden role in the cellular processes associated with oncolines and their vital function in the apoptotic process, cell cycle regulation, and autophagy. The article provides a comprehensive summary of the evidence base for targeting USPs as potential factors for neoplasm treatment. The review considers the participation of the UPS system in the development, resulting in the importance of p53, Rb, and NF-κB, and evaluates specific goals for therapeutic administration using midnight proteasomal inhibitors and small molecule antagonists of E1 and E2 enzymes. Despite the slowed rate of drug creation, recent therapeutic discoveries based on USP system dynamics hold promise for specialized therapies. The review concludes with an analysis of future wanderers and the feasible effects of targeting USPs on personalized GB therapies, which can improve patient hydration in this current and unattractive therapeutic landscape. The manuscript emphasizes the possibility of USP oncogene therapy as a promising alternative treatment line for GB. It stresses the direct creation of research on the medical effectiveness of the approach.