This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal and endometrial cancer. P285R is the most common recurrent mutation of POLE in those types of cancers. Somatic POLE mutation is associated with approximately 3% of sporadic microsatellite-stable (MSS) but hypermutated CRCs.