CENPO is a component of the CENPA-CAD (nucleosome distal) complex, which is recruited to centromeres and is involved in the assembly of kinetochore proteins, mitotic progression and chromosome segregation. It may also contribute to the incorporation of newly synthesised CENPA into centromeres through its interaction with the CENPA-NAC complex. In addition, CENPO modulates the kinetochore-bound levels of the NDC80 complex.

The CENPO protein is found in the nucleus and at the centromere, including the kinetochore. According to the NCBI Gene summary, it is localised to the centromere throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation and checkpoint signalling during mitosis. The CENPO gene belongs to the HGNC group of constitutive centromere associated network genes, and the protein belongs to the CENP-O/MCM21 family. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed.

CENPO is also known as CENP-O and by the earlier alias MGC11266. Mouse has an orthologous gene, Cenpo. Because the protein sits at the interface between centromeric chromatin and the kinetochore machinery, it is a useful subject for studies of how centromere identity is maintained and how chromosomes are accurately distributed during cell division.