In our previous report (27), we also demonstrated that the polβ/XRCC1 complex enhances the handoff of nicked repair products to the final ligation step and XRCC1 cancer-associated (P161L, R194W, R280H, R399Q, Y576S) and cerebellar ataxia–related (K431N) variants impact this channeling process distinctly depending on the nature of the mutation. Here, POLB is linked to aceruloplasminemia.