MSL1 (male-specific lethal 1) is a non-catalytic scaffold protein of the MSL histone acetyltransferase complex that mediates histone H4 acetylation at lysine 16 (H4K16ac), an epigenetic mark preventing chr17 compaction 123. Within the complex, MSL1 tethers MSL3 and KAT8 together to regulate enzymatic activity 4 and greatly enhances MSL2 E3 ubiquitin ligase activity, promoting H2B monoubiquitination at lysine 34, which stimulates H3K4 and H3K79 methylation and gene activation 56. MSL1 maintains chromosome 17 and genome integrity through homeostatic H4K16ac levels 3. Beyond canonical histone acetylation, MSL1 participates in DNA damage responses by interacting with Nupr1 and 53BP1 to facilitate DNA repair following gamma-irradiation 78. Two distinct nuclear localization signals regulate MSL1 subcellular distribution and function in regulating KAT8 activity 9. In colon cancer, MSL1 promotes ferroptosis through the KCTD12-SLC7A11 axis, suggesting therapeutic relevance 10. These findings establish MSL1 as a multifunctional chr17 regulator controlling both gene expression and cellular stress responses.