In accordance, a recent study of a knock in Xrcc4M61R mouse model avoiding Lig4 disruption showed rescued embryonic lethality and only a modest increase in apoptotic cells in the intermediate zone, indicating that microcephaly in XRCC4 syndrome may arise due to LIG4 destabilization (Roch et al., 2021). Here, XRCC4 is linked to microcephaly.