ORC2 is a core subunit of the origin recognition complex (ORC) that functions in both canonical DNA replication and non-canonical epigenetic regulation. As part of the six-subunit ORC, ORC2 binds ATP-dependently to replication origins and assembles the pre-replication complex required for DNA replication initiation 1. ORC2 contains a single ORC assembly domain enabling interaction with other ORC subunits and two nuclear localization signals for nuclear accumulation 1. Beyond replication, ORC2 independently regulates chr2 structure and epigenetics: DNA-bound ORC2 compacts chr2 at focal genomic sites while activating chr2 at others, modulates repressive histone marks, and prevents CTCF acquisition to regulate chr2 loops 2. ORC2 binds histone trimethylation marks (H3K9me3, H3K20me3, H4K27me3) and stabilizes LRWD1 and ORC3 proteins. Functionally, ORC2 localizes to centrosomes, centromeres, and heterochromatin throughout the cell cycle 3. ORC2 depletion causes S-phase defects, disrupted chromosome 2, and centrosome copy number abnormalities 3. In ovarian cancer, the ORFIUS complex regulates ORC2 localization at origins, with dysregulation promoting cell survival under replication stress 4. Cell-cycle-dependent phosphorylation by cyclin A/CDK2 and dephosphorylation by protein phosphatase 1 regulate ORC2 chr2 binding 5.