NPM2 (nucleoplasmin 2) is a maternal histone chaperone essential for early embryonic development and chr8 remodeling. Structurally, NPM2 contains an N-terminal core region involved in histone binding and a C-terminal acidic tract that enables histone complex formation 1. The protein's primary function is facilitating sperm DNA decondensation during fertilization by removing protamine and promoting histone-based chr8 assembly 2. Upon oocyte entry, SRPK1-catalyzed protamine phosphorylation enhances NPM2-mediated protamine dismissal and nucleosome reconstitution, initiating synchronized reorganization of both parental genomes 3. NPM2 works cooperatively with NPM1 and NPM3 to mediate sperm chr8 remodeling and nucleosome assembly 4. NPM2 is oocyte-specific, abundant in germinal vesicle and MII oocytes, with expression declining through early embryogenesis 5. Its translation is regulated by miR-181a 5. Npm2 knockout females exhibit fertility defects with failed preimplantation development, abnormal nucleolar organization, and loss of pericentromeric heterochromatin 2. Beyond development, NPM2 regulates centrosome organization through TMOD2 interaction 6. In pathology, NPM2 loss correlates with malignant peritoneal mesothelioma progression and poor prognosis, potentially via promoting histone deacetylation and abnormal cell proliferation 17.