AP endonuclease (AP endonucleases) are key enzymes in the DNA repair mechanism, primarily including APE1 and APE2. These enzymes are responsible for cutting the phosphate backbone after removing apurinic/apyrimidinic sites in DNA. AP endonucleases are predominantly located in the nucleus and are involved in the base excision repair (BER) pathway, crucial for maintaining genomic stability. APE1 is ubiquitously expressed, while APE2 expression is more limited. Mutations or functional deficiencies in AP endonucleases are associated with various cancers and genetic diseases.