NAP1L2 is an X-linked histone chaperone that regulates chrX accessibility and gene expression through histone acetylation control 1. The protein plays critical roles in cellular differentiation, particularly in neuronal and osteogenic lineages. During neuronal development, NAP1L2 promotes histone acetylation at target genes like Cdkn1c, facilitating neuronal differentiation and preventing excessive neural stem cell proliferation 23. Conversely, elevated NAP1L2 expression during aging suppresses osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by recruiting SIRT1 to deacetylate histone H3 lysine 14 (H3K14ac) at osteogenic gene promoters (Runx2, Sp7, Bglap), thereby promoting BMSC senescence 1. NAP1L2 dysfunction has disease relevance across multiple contexts: genetic variants in its CpG-rich promoter region associate with neural tube defects 4, while dysregulation correlates with neurodegenerative disease progression 5. In cancer, NAP1L2 mRNA stabilization by m6A methylation promotes prostate cancer malignancy through MMP pathway activation 6, and elevated expression appears in colorectal cancer diagnostic panels 7. Additionally, NAP1L2 participates in diabetic cardiomyopathy pathogenesis via periostin-mediated BCAA catabolism impairment 8. These findings establish NAP1L2 as a multifunctional chrX regulator with significant clinical implications in aging, neurological disease, and cancer.