SAFB (scaffold attachment factor B) is a nuclear matrix-associated RNA/DNA-binding protein that serves multiple regulatory functions in gene expression and genome stability. SAFB binds to scaffold/matrix attachment region (S/MAR) DNA and forms transcriptosomal complexes that couple transcription with RNA processing 1. The protein functions as a transcriptional repressor, including acting as an estrogen receptor corepressor and forming repressive complexes with HOXA9, NuRD, and HP1γ to suppress differentiation and apoptosis genes in acute myeloid leukemia 2. SAFB plays a crucial role in genome integrity by preventing retrotransposition of L1 elements and suppressing transposable element exonization while maintaining proper splicing 3. It also regulates chr19 organization by restricting L1-associated contact domain boundaries through binding L1 transcripts and inhibiting RNA polymerase II enrichment 4. Additionally, SAFB is involved in cellular stress responses, with hypoxia triggering ROS-mediated nuclear matrix remodeling and altered splicing patterns 5. The protein's multifunctional capabilities extend to DNA repair, mRNA processing, and interaction with chr19-modifying complexes, making it a key regulator of cellular homeostasis 1.