YEATS4 is a chr12 reader component of the NuA4 histone acetyltransferase complex that recognizes and binds acetylated histone H3, particularly H3K18ac/H3K27ac and H3K14ac/H3K27ac patterns 123. YEATS4 also reads histone crotonylation, specifically H3K14cr, linking this modification to metabolic gene activation 4. A key mechanistic function involves recruiting the NuA4-related complex to deposit histone variant H2A.Z at promoters of actively transcribed genes, essential for embryonic stem cell maintenance 1. YEATS4 acetylation by KAT8 stabilizes the protein by preventing HUWE1-mediated ubiquitination and degradation 5. Clinically, YEATS4 dysregulation associates with multiple malignancies. High YEATS4 expression correlates with poor bladder cancer prognosis and reduced cisplatin sensitivity 5, while YEATS4 knockdown suppresses glioblastoma and colorectal cancer cell proliferation and promotes apoptosis 67. In breast cancer, YEATS4 promotes stem cell properties and fatty acid metabolism through H3K14cr reading 4. Conversely, germline YEATS4 mutations predispose to uterine leiomyoma through defective H2A.Z deposition 8. A YEATS4 regulatory variant (rs622656-C) confers protection against tuberculosis immune conversion, suggesting YEATS4 involvement in innate lymphoid cell differentiation 9. These findings position YEATS4 as a critical epigenetic regulator with substantial therapeutic potential.