Our transcriptome and in vitro data revealed significant insights into FOSL1’s orchestration of the NF-κB signaling pathway, enhancing NF-κB’s activity while reducing the protein levels of p53 and PTEN protein in glioma cell lines featuring wild type p53 (wtp53) and/or PTEN (wtPTEN). The gene discussed is NFKB1; the disease is central nervous system cancer.