BEX2 is an X-linked gene encoding a multifunctional regulatory protein with prominent roles in cancer cell survival and proliferation. Functionally, BEX2 acts as a mitochondrial apoptosis inhibitor and cell cycle regulator in cancer cells, primarily through modulation of anti-apoptotic (BCL2) and pro-apoptotic (BAD, BAK1, PUMA) BCL2 family members, and regulation of G1 phase through CCND1 and CDKN1A 1. In non-small cell lung cancer, crotonylated BEX2 at K59 enhances chemotherapy resistance by promoting mitophagy via facilitating NDP52-LC3B interaction 2. BEX2 further regulates autophagy in NSCLC by inhibiting PI3K/AKT/mTOR signaling through PIK3CA-p85 interaction disruption 3. Disease relevance is substantial: BEX2 demonstrates pro-oncogenic function across multiple malignancies including breast, colorectal, hepatocellular, and brain tumors, with cross-talk involving NF-κB and JNK/c-Jun pathways 4. In gastric cancer, BEX2 promotes cancer stemness and cisplatin resistance via CHRX upregulation 5. BEX2 operates within feedback loops with c-Jun/p65, regulating their phosphorylation and activity 6. Under reductive stress conditions, BEX2 acts as a pseudosubstrate inhibitor of the CRL2(FEM1B) ubiquitin ligase complex, protecting FNIP1 from degradation 7. Clinically, BEX2 overexpression associates with poor prognosis in lymph node metastasis-free lung adenocarcinoma, supporting BEX2 as a therapeutic target.