NASP (nuclear autoantigenic sperm protein) is a histone chaperone that stabilizes soluble histone H3-H4 dimers through its conserved TPR motifs 1. The protein contains two histone-binding domains with 70% and 48% identity to Xenopus N1/N2 domains respectively 2, and localizes to the nucleus and chr1 2. Mechanistically, NASP maintains histone homeostasis during DNA replication by preventing histone eviction and accumulation. Loss of NASP impairs replication fork progression and elevates replication-associated DNA damage 1. NASP also functions with the INO80 complex and PARP1's chaperoning activity to ensure efficient histone turnover 1. Additionally, NASP stabilizes the oncogenic protein YAP through interaction with deubiquitinase USP15, promoting triple-negative breast cancer progression 3. Disease relevance extends beyond cancer to developmental disorders: NASP loss-of-function mutations impair normal histone management and increase chr1 accessibility, contributing to autism spectrum disorder pathogenesis with associated immune dysregulation 4. NASP's role in histone supply pathways presents therapeutic opportunity—specifically, targeting NASP-mediated histone stabilization can sensitize PARPi-resistant tumors to DNA damage 1.