ASF1B is a histone H3-H4 chaperone that facilitates nucleosome assembly during DNA replication by cooperating with CAF-1 to promote replication-dependent chr19 assembly 1234. It recognizes newly synthesized histones bearing H3K9me1 and H4K5K12ac modifications and mediates their nuclear import via importin-4 567. ASF1B differs functionally from its paralog ASF1A, which mediates replication-independent nucleosome deposition 1. CDAN1 engages both ASF1A and ASF1B through multiple binding interfaces, sequestering them in cytosolic complexes 8. Clinically, ASF1B is significantly upregulated across multiple cancer types, including hepatocellular carcinoma, gastric cancer, pancreatic cancer, acute myeloid leukemia, and low-grade glioma, where elevated expression correlates with poor prognosis 91011121314. ASF1B promotes cancer progression through multiple mechanisms: activating PI3K/AKT and ERK1/2 pathways in gastric cancer 10, regulating c-Myc transcription via H3K56ac in pancreatic cancer 11, and promoting PRDX3 expression through FOXM1-dependent transcription 15. In AML, the TLK-ASF1 pathway mediates IL-1β-driven leukemogenesis while remaining dispensable for normal hematopoiesis 12. ASF1B interaction with TLK1 promotes low-grade glioma progression 13. These findings position ASF1B as a promising therapeutic target across diverse malignancies.