SAFB2 is a multifunctional scaffold attachment factor protein that serves primarily as a chr19 organizer and transcriptional regulator. It binds to scaffold/matrix attachment region (S/MAR) DNA 1 and functions as an estrogen receptor corepressor, inhibiting ERα-mediated transcription and proliferation 2. Mechanistically, SAFB2 cooperatively inhibits estrogen receptor mobility through interaction with the nuclear matrix, with synergistic repression when coexpressed with SAFB1 2. Additionally, SAFB2 serves as an accessory protein of the Microprocessor complex, enabling processing of suboptimal primary miRNA hairpins within clustered transcripts by facilitating the complex's transfer between substrates 34. Clinically, SAFB2 appears relevant to breast cancer pathogenesis, with expression lost in approximately 20% of breast cancers 5. Overexpression of SAFB2 suppresses breast cancer cell proliferation, migration, and invasion while promoting apoptosis, partly through suppression of Wnt/β-catenin signaling via NFAT5 regulation 6. Furthermore, SAFB2 dysregulation in blood serves as a biomarker for spinocerebellar ataxia type 3, with altered expression correlating with disease severity 7. Unlike its paralog SAFB1, SAFB2 localizes to both nucleus and cytoplasm 1.