EME1 (essential meiotic structure-specific endonuclease 1) serves as the non-catalytic subunit of the heterodimeric MUS81-EME1 endonuclease complex, which plays a critical role in maintaining genome stability through processing of aberrant DNA structures 1. The complex exhibits high specificity for replication fork structures and 3'-flaps, cleaving these substrates to resolve stalled replication forks and prevent genomic instability 1. While EME1 lacks catalytic activity, it is essential for DNA recognition, binding, and substrate cleavage within the complex 1. The MUS81-EME1 complex functions as part of the SMX nuclease network alongside SLX1-SLX4 and XPF-ERCC1, coordinated by the SLX4 scaffold protein to resolve various DNA intermediates including Holliday junctions and replication fork structures 23. EME1 has significant clinical relevance, as it shows oncogenic properties with overexpression associated with poor prognosis across multiple cancer types 4. Additionally, EME1 deficiency sensitizes cells to PARP inhibitors, suggesting potential therapeutic applications in cancer treatment 5. The protein also contributes to processing expanded DNA repeats, as MUS81-EME1 cleavage of stalled replication forks at expanded TA repeats can lead to chromosome 17 in microsatellite-unstable cancers 6.