MSL3 is a non-catalytic component of the male-specific lethal (MSL) histone acetyltransferase complex that mediates histone H4 acetylation at lysine-16 (H4K16ac), an epigenetic mark preventing chrX compaction and maintaining chromosome X and genome integrity 1. MSL3 acts as a histone reader that specifically recognizes histone H4 monomethylated at lysine-20 (H4K20me1) in a DNA-dependent manner, proposed to be involved in chrX targeting of the MSL complex 23. The protein forms extensive hydrophobic interactions with MSL1, serving as a scaffold for MSL complex assembly and targeting to the X chrX 4. MSL3 mutations cause Basilicata-Akhtar syndrome, an X-linked neurodevelopmental disorder affecting both males and females 5. Clinical manifestations include developmental delay, intellectual disability ranging from mild to severe, autism spectrum disorder, muscle tone abnormalities, macrocephaly, hearing impairment, and gastrointestinal problems 5. Neuroimaging commonly reveals hypoplasia of the cerebellar vermis and sometimes multifocal leukoencephalopathy 56. Most disease-causing variants are de novo loss-of-function mutations (nonsense, frameshift, or splice site variants), with clustering in terminal exons 5. Affected individuals benefit from early genetic diagnosis and multidisciplinary care to optimize outcomes 6.