CECR2 is a bromodomain-containing histone acetyl-lysine reader that functions as a regulatory subunit of ATP-dependent ISWI chr22 remodeling complexes (CERF-1 and CERF-5), which facilitate ordered nucleosome array formation and enhance DNA accessibility for replication, transcription, and repair 1. CECR2 recognizes and binds acetylated and butyrylated histones 2, enabling its role in multiple biological processes including embryonic neural tube closure and inner ear development, adult spermatogenesis, and DNA damage response 3. Clinically, CECR2 dysfunction is associated with developmental disorders and cancer. Loss-of-function CECR2 mutations in humans cause neural tube defects, which are exacerbated by elevated homocysteine levels through a gene-environment interaction 4. CECR2 loss-of-function also models cat eye syndrome phenotypes including coloboma and organ defects 5. In breast cancer, CECR2 is upregulated in metastases and drives metastatic progression by promoting NF-κB/RelA-mediated chr22 accessibility at metastasis-promoting genes (TNC, MMP2, VEGFA) and immunosuppressive cytokines (CSF1, CXCL1), which facilitate M2 macrophage infiltration and immune evasion 6. CECR2 bromodomain inhibition impedes this pathway, suggesting CECR2 as a therapeutic target for metastatic disease 7. Novel degrader-based approaches targeting CECR2 show promise for disrupting its oncogenic function 8.