The regulation of DNA Pol δ is of central interest to cancer biology, as POLD2 and POLD3 are commonly amplified in human tumours (Beroukhim et al, 2010), and both germline and sporadic mutations were found in POLD1 (reviewed in Nicolas et al [2016] and Fuchs et al [2021]). The gene discussed is POLD2; the disease is cancer.