ZBTB24 is a BTB-zinc finger transcription factor that plays critical roles in DNA methylation, immune function, and transcriptional regulation. The protein contains a BTB domain, AT-hook, and eight C2H2 zinc finger motifs, with the last four zinc fingers (ZF5-8) conferring DNA-binding specificity to a 12-bp consensus sequence [CT(G/T)CCAGGACCT] 1. ZBTB24 localizes to heterochromatin through its AT-hook and zinc finger domains, particularly the 6th motif, and activates transcription via the 6th and 7th zinc finger motifs 2. A key function is regulating CDCA7 expression, another ICF syndrome gene, through direct promoter binding 2. ZBTB24 is essential for establishing and maintaining DNA methylation patterns at centromeric satellite repeats by recruiting DNMT3B 3. In immune cells, ZBTB24 prevents T-cell apoptosis by regulating the CDCA7/TRAIL-receptor axis, with deficiency leading to upregulation of TRAIL death receptors 4. Mutations in ZBTB24 cause ICF syndrome type 2, characterized by immunodeficiency, centromeric instability, and facial anomalies 5. Patients exhibit hypogammaglobulinemia, reduced T-cell function, and chr6 instability with distinctive multiradial chr6 6. The protein also plays roles in trophoblast development and DNA repair mechanisms 7.