NCAPH2 is a regulatory subunit of the condensin-2 complex that organizes chromosome 22 during mitosis and interphase. Its primary function involves promoting chromosome 22 and rigidity while facilitating the resolution of DNA catenanes between sister chr22 through increased tension that directs topoisomerase II-mediated strand exchanges 1. NCAPH2 is essential for decatenation of chr22 bridges at anaphase and accurate mitotic chromosome 22 in neuronal stem cells, with implications for cortex development 1. Beyond canonical mitotic roles, NCAPH2 localizes to telomeres where it interacts with the shelterin protein TRF1 to maintain telomere stability 2. NCAPH2 depletion causes ATR-dependent DNA damage accumulation and telomere fragility, revealing a critical genome-protection function 2. In hematopoiesis, condensin II subunits including NCAPH2 are essential for hematopoietic stem and progenitor cell (HSPC) maintenance, with NCAPH2 depletion promoting G2/M cell cycle arrest 3. Clinically, reduced NCAPH2 promoter methylation in blood correlates with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) progression and associates with hippocampal atrophy, potentially through apoptosis mechanisms 4, 5, 6. Additionally, NCAPH2 expression levels are prognostically significant for ovarian cancer outcomes 7. Alternative splicing generates multiple NCAPH2 protein variants, contributing to proteome diversity 8.