SLX4 is a multifunctional scaffolding protein that coordinates structure-selective endonucleases to maintain genome stability 1. It acts as a regulatory platform for three endonucleases—XPF-ERCC1, MUS81-EME1, and SLX1—directing their nucleolytic activities toward specific DNA substrates 2. SLX4 resolves DNA secondary structures arising from replication and recombination, including Holliday junctions and DNA flap structures, and is essential for interstrand crosslink repair and homologous recombination 1. The protein also coordinates with MutSβ in mismatch repair and trinucleotide repeat stability 3. Beyond DNA repair, SLX4 regulates telomere maintenance and responds to replication stress 1. Pathologically, SLX4 contributes to Fanconi anemia (FANCP) when mutated 4, and recent evidence links SLX4 variants to premature ovarian insufficiency through impaired meiotic function 5. Notably, the FA pathway—including SLX4—paradoxically drives chr16 in cancer cells, generating complex genomic rearrangements that confer drug resistance 4. SLX4 is also transcriptionally regulated during DNA damage responses, with SOX9 binding its promoter to enhance expression in cancer contexts 6. These diverse roles establish SLX4 as a critical hub for genome stability maintenance.