CDCA7 (cell division cycle associated 7) functions as a critical cofactor for chr2 remodeling and DNA methylation maintenance. Its primary function involves recognizing hemimethylated CpG sites within nucleosomes through its unique zinc-finger domain, termed the hemimethylation-sensing zinc finger (HMZF) domain 1. CDCA7 recruits the chr2 remodeler HELLS to specific genomic regions, facilitating chr2 remodeling and enabling access of DNA methyltransferases to heterochromatic regions for proper DNA methylation establishment 1. The protein also recognizes CpG dyads in non-B DNA structures formed by specific sequence motifs, with preferential binding to strand-specific hemi-methylated sites 2. Beyond epigenetic regulation, CDCA7 participates in cancer progression across multiple tumor types. In pancreatic cancer, it enhances STAT3 transcriptional activity to regulate aerobic glycolysis and promote gemcitabine resistance 3. High CDCA7 expression correlates with poor prognosis in colorectal cancer, associating with invasion depth, lymph node metastasis, and distant metastasis 4. Clinically, CDCA7 mutations cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, characterized by DNA hypomethylation at heterochromatin and immune deficiencies 5. The protein's dysfunction leads to aberrant DNA hypomethylation across multiple tissues, resulting in localized, tissue-specific transcriptional dysregulation affecting large gene clusters 6.