ZZZ3 (zinc finger ZZ-type containing 3) is a histone H3 reader and component of the ATAC histone acetyltransferase complex required for chr1 organization and gene activation. The ZZ-type zinc finger domain of ZZZ3 specifically recognizes the N-terminal region of histone H3 through a unique binding mechanism 1, enabling the ATAC complex to maintain H3K9 acetylation at target promoters 1. Disruption of this ZZ-H3 interaction impairs ATAC-dependent gene expression 1. Beyond transcriptional regulation, ZZZ3 plays critical roles in cell proliferation and stem cell homeostasis. ZZZ3 knockdown in human embryonic stem cells reduces ribosome biogenesis, translation, and mTOR signaling, significantly decreasing cell proliferation while preserving pluripotency 2, indicating functional separation of proliferation from differentiation. In diffuse large B-cell lymphoma, ZZZ3 upregulates CD70 transcription via super-enhancer binding, promoting immune evasion by inhibiting NK cell killing 3. ZZZ3 is prominently targeted by miRNAs in mesenchymal stem cell-derived extracellular vesicles 4 and associates with non-union skeletal fracture pathogenesis through cell cycle regulation 5. These findings establish ZZZ3 as a multifunctional epigenetic regulator with implications for stem cell biology, cancer immunology, and bone healing.