BEX3 is an X-linked protein with pleiotropic roles in neuronal survival, reductive stress regulation, and cancer suppression. Structurally, BEX3 forms high-order oligomers with partially folded regions and a proteolysis-resistant core 1. In neuronal development, BEX3 enhances NGF-mediated survival by directly binding the trkA promoter to increase TrkA receptor expression; BEX3 downregulation increases apoptosis in NGF-deprived sensory neurons 2. BEX3 functions as a pseudosubstrate inhibitor of the CUL2FEM1B ubiquitin ligase, using zinc as a molecular glue to prevent premature degradation of FNIP1 during reductive stress, thereby protecting cells from pathological ROS depletion 3. Unlike its family member BEX2 (an oncogene), BEX3 acts as a tumor suppressor—overexpression inhibits breast cancer tumor formation in xenograft models 4. BEX3 emerged through transposon domestication and is enriched in the CNS with neural-specific functions; alterations in BEX3 expression correlate with developmental competence in human embryos and are associated with neurological disorders including autism and schizophrenia 5. Recent evidence links BEX3 overexpression to hypoxia and poor survival in proficient mismatch repair gastric cancers 6, suggesting context-dependent roles in disease pathogenesis.