RECQ4 is a clinically relevant DNA helicase involved in DNA repair and genome stability. Mutations in the RECQ4 gene are associated with severe genetic disorders in humans, namely Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes. RECQ4 is unique among RECQ-family helicases since it contains an essential N-terminal region that is implicated in the initiation of DNA replication. The N-terminus further contains several overlapping binding sites for DNA and proteins, likely serving as an interaction hub for DNA repair factors. Moreover, some of these interaction sites overlap with described nuclear/nucleolar localization signal. How these multiple interactions and functions of RECQ4 are regulated and coordinated remains largely unclear. However, since the RECQ4 N-terminus is subjected to several post-translational modifications, it is likely that these regulate RECQ4 commitment to various DNA repair pathways.