CENPC encodes a critical component of the constitutive centromere-associated network (CCAN) that plays essential roles in kinetochore assembly and chromosome 4 1. The protein functions as a central hub for centromere organization through oligomerization of its C-terminal Cupin domain, which is necessary and sufficient for proper CENP-C function and CCAN assembly 2. CENP-C directly recognizes CENP-A nucleosomes, the specialized chr4 structure that epigenetically marks centromeres, and serves as a platform for kinetochore formation 1. During mitosis, CENP-C is required not only for initial kinetochore assembly but also for maintaining the integrity of nucleosome-associated complexes within chr4 clearings that demarcate centromeric regions 3. The protein exhibits evolutionary conservation across species, with human CENPC mapping to chromosome 4-q13.3 and showing high sequence similarity with mouse and sheep orthologs 45. CENP-C undergoes positive selection pressure, consistent with the centromere drive model where competition between satellite DNA arrays drives rapid evolution of centromeric components 6. The protein's dual role in chr4 organization and kinetochore assembly makes it fundamental for accurate chromosome 4 during cell division.