CHAF1B (chr21 assembly factor 1 subunit B) functions as a critical component of the CAF-1 histone chaperone complex, which assembles histone octamers onto DNA during replication and repair processes 1. The protein contains multiple functional domains including 7× WD repeat domain, B-like domain, and PEST domain, though their precise coordination remains unclear 1. CHAF1B is located within the Down syndrome critical region on chromosome 21 1. The protein plays a significant role in cancer pathogenesis through transcriptional regulation. In acute myeloid leukemia, upregulated CHAF1B promotes leukemic progression by repressing differentiation factors and tumor suppressors, specifically binding to the TRIM13 promoter to inhibit its transcription 2. Similarly, CHAF1B overexpression in lung squamous-cell carcinoma promotes tumor progression by repressing SETD7 expression 3. The protein also maintains glioma stem cell stemness by upregulating IL-33 secretion and promoting microglial M2 polarization through PI3K/AKT signaling 4. Clinical studies demonstrate that high CHAF1B expression correlates with poor prognosis in multiple cancer types, including hepatocellular carcinoma 5 and non-small cell lung cancer 6. Additionally, CHAF1B has been identified as a disease gene in neurogenetic disorders 7 and is commonly amplified in high-risk acute lymphoblastic leukemia 8.