ERCC6L is an X-linked DNA helicase functioning as a tension sensor for catenated DNA during mitosis 1. It acts as an ATP-dependent DNA translocase capable of promoting Holliday junction branch migration in vitro 12. During anaphase, ERCC6L marks ultrafine DNA bridges and coordinates with RAD52 to maintain genome stability; depletion of either factor increases DNA bridges and genome instability, particularly under replication stress 3. ERCC6L has emerged as a significant oncogenic driver in multiple cancers. In colorectal cancer, ERCC6L overexpression correlates with tumor size and promotes cell proliferation, cycle progression, and invasion; knockdown inhibits these phenotypes and arrests cells in G0/G1 phase 4. In lung adenocarcinoma, elevated ERCC6L associates with poor prognosis and enhances glycolysis and stemness through HIF-1α stabilization and activation 56. In gastric cancer, ERCC6L facilitates growth and metastasis via NF-κB signaling activation 7. Conversely, ERCC6L2 (a related protein) acts as a tumor suppressor, regulating DNA end resection extent through phase separation-mediated CtIP condensates; downregulation correlates with ATM inhibitor resistance 8. These findings position ERCC6L/ERCC6L2 as potential biomarkers and therapeutic targets.