RECQL4 is an ATP-dependent 3'-5' DNA helicase that unwinds double-stranded DNA with 3' overhangs, processing up to 18 bp of dsDNA 1. Its N-terminal domain preferentially binds Y-shaped DNA structures 2, while the core helicase domain binds single-stranded DNA 1. RECQL4 maintains genomic stability through diverse functions including DNA replication initiation, telomere maintenance, double-strand break repair via homologous recombination, and nucleotide excision repair 3. Loss-of-function RECQL4 mutations cause three autosomal recessive syndromes: Rothmund-Thomson syndrome (RTS), RAPADILINO, and Baller-Gerold syndrome (BGS), characterized by developmental defects, premature aging features, and cancer predisposition 4. RTS patients, particularly RTSII with RECQL4 mutations, show increased osteosarcoma risk in childhood and skin cancer later in life 5. Conversely, elevated RECQL4 expression in sporadic cancers, including hepatocellular carcinoma, reduces radiotherapy sensitivity by enhancing DNA repair and suppressing anti-tumor immune responses through the cGAS-STING pathway 6. These dual roles—protective in inherited deficiency contexts but oncogenic when overexpressed—position RECQL4 as both a genomic stability guardian and a potential cancer therapeutic target 4.