BEND2 (BEN domain containing 2) is an X-linked nuclear protein involved in DNA binding and protein interactions 1. Primary function: BEND2 acts as a transcriptional regulator recognizing specific DNA motifs 1. In normal development, full-length BEND2 is critical for establishing the ovarian reserve during oogenesis, though it is dispensable for male spermatogenesis 2. The smaller BEND2 isoform appears sufficient for spermatogenesis 2. Disease relevance: BEND2 is implicated in multiple cancers through gene fusion events. MN1-BEND2 fusions initiate astroblastoma specifically in ventral telencephalon neural progenitors, converging with other ABM-associated fusions on shared DNA motifs and downstream gene regulation including PDGFRα pathway activation 1. Similar MN1-BEND2 fusions occur in ependymal tumors with good prognosis in female children 3 and recurrent spinal cord astroblastomas 4. CHD7::BEND2 and EWSR1::BEND2 fusions are detected in aggressive pancreatic neuroendocrine tumors, independently predicting poor prognosis 5. EWSR1::BEND2 has also been identified in bladder sarcomas 6. Clinical significance: BEND2 alterations serve as independent negative prognostic biomarkers in PanNETs 5, and BEND2 variants are candidate genes in nonobstructive azoospermia 7.