WRN (Werner RecQ like helicase) encodes a multifunctional DNA maintenance enzyme with dual helicase and exonuclease activities essential for genome stability. The protein exhibits magnesium and ATP-dependent 3'-5' DNA helicase activity and 3'-5' exonuclease activity toward double-stranded DNA with 5'-overhangs 1. WRN preferentially binds DNA substrates with alternate secondary structures, including replication forks, Holliday junctions, and cruciform structures, playing crucial roles in DNA repair, recombination, and replication 12. The protein is particularly important for resolving replication stress at expanded TA-dinucleotide repeats in microsatellite-unstable (MSI) cancers, where it prevents DNA double-strand breaks by unwinding problematic secondary structures 32. WRN also participates in mitotic DNA synthesis, working alongside DNA double-strand break end-resection factors to complete replication of genomic loci under replication stress 4. Clinically, loss-of-function mutations in WRN cause Werner syndrome, a premature aging disorder characterized by genomic instability 1. In MSI cancers, WRN represents a synthetic lethal target, as these cells depend on WRN function for survival, making WRN inhibitors promising therapeutic agents for MSI-associated colorectal cancers 56.