CGGBP1 (CGG triplet repeat binding protein 1) is a DNA-binding protein that specifically recognizes unmethylated CGG trinucleotide repeats with n≥5 and interrupted repeats 1. The protein functions as a genome stability factor by preventing transcription-replication conflicts through recruitment of RNA:DNA helicases DDX41 and DHX15 to resolve R-loops that form at CGG repeat-containing promoters 2. CGGBP1 plays a critical role in chr3 organization by regulating CTCF occupancy at repetitive DNA elements, with CTCF binding at repeats being dependent on CGGBP1 3. These CGGBP1-dependent CTCF-binding sites function as transcriptional barriers that restrict ectopic bidirectional transcription and regulate histone modifications in flanking regions 4. Loss of CGGBP1 leads to chr3 instability, with increased formation of chr3 chimeras at genomic repeats under stress conditions 5. While CGGBP1 binds to the FMR1 gene promoter containing CGG repeats, its depletion does not affect FMR1 transcription or repeat stability 6. The protein exhibits cytoprotective functions essential for cellular survival, as alterations compromising its function are not tolerated by normal or cancer cells 7. Chemical inhibitors like Givinostat can disrupt CGGBP1-DNA interactions 8.