Current knowledge about the role of the cellular ubiquitin–proteasome system dysregulation, and subsequent NFKB activation in periodontitis, is still limited, but it may explain the presence of the E3 ubiquitin-protein ligase (CBL) gene among the leader genes in the genetic linkage between periodontitis and CRC, although no evidence is available relating CBL to periodontitis [20]. This evidence concerns the gene NFKB1 and periodontitis.