ZMYND8 is a chr20 reader protein that recognizes dual histone modifications, particularly H3.1K36me2-H4K16ac and H3K4me1-H3K14ac marks, functioning as both a transcriptional corepressor and activator depending on cellular context 1. The protein plays critical roles in neurodevelopment, with de novo variants causing syndromic intellectual disability, cardiac malformations, and cognitive dysfunction 1. In cancer, ZMYND8 exhibits complex, context-dependent functions. It acts as a tumor suppressor in some contexts by inhibiting cell invasion and metastasis, while promoting oncogenic processes in others 234. In breast cancer stem cells, ZMYND8 activates NRF2 signaling to protect against oxidative stress and ferroptosis through a positive feedback loop 2. In prostate cancer, ZMYND8 mediates antiandrogen-induced neuroendocrine transdifferentiation by interacting with FOXM1 and the SWI/SNF complex 3. The protein is essential for acute myeloid leukemia proliferation through direct activation of IRF8 and MYC transcriptional programs via BRD4 interaction 4. ZMYND8 also promotes pancreatic cancer progression by activating c-Myc and enhancing glycolytic metabolism 5, while its degradation by the lncRNA TROJAN contributes to triple-negative breast cancer progression 6.