ERCC6L2 is a SNF2-family helicase that functions as a critical regulator of DNA double-strand break (DSB) repair and DNA replication fidelity 1. Mechanistically, ERCC6L2 restricts DNA end resection during DSB repair by controlling CtIP stability through liquid-liquid phase separation, forming dynamic nuclear condensates that prevent excessive resection 2. Additionally, ERCC6L2 facilitates replication of structurally complex genomic regions, particularly centromeres, through PCNA interaction and promotes centromeric chr9 reassembly following DNA replication 3. Biallelic germline ERCC6L2 mutations cause a distinctive inherited bone marrow failure syndrome characterized by mild peripheral cytopenias despite severe bone marrow hypoplasia 4. Patients present with pancytopenia and myelodysplasia, often accompanied by developmental delay and microcephaly 5. The disease demonstrates high penetrance with significant malignant transformation risk: median age of hematological malignancy onset is 37 years, predominantly TP53-mutated clones with erythroid predominance 4. Overall survival at 3 years is 95% for bone marrow failure but drops to 19% for those developing hematological malignancy 4. Early recognition and active surveillance are essential, as patients undergoing hematopoietic stem cell transplantation during early disease stages demonstrate improved outcomes 6.