RMI2 (RecQ mediated genome instability 2) is an essential component of the BTR (BLM-TopoisomeraseIIIα-RMI1-RMI2) complex that plays a critical role in DNA repair and genome stability. Mechanistically, RMI2 is required for the stability, localization, and function of BLM and TOP3A, targeting these proteins to chr16 and stress-induced nuclear foci 1. The RMI2-containing TRR complex catalyzes resolution of DNA recombination intermediates and Holliday junctions, with RMI2 regulating the gate-opening mechanism that allows duplex DNA transfer 1. The complex also suppresses alternative lengthening of telomeres by ameliorating replication stress 2. Clinically, RMI2 dysregulation is associated with multiple cancer types. RMI2 is markedly upregulated in hepatocellular carcinoma, breast cancer, and other tumors, where high expression correlates with poor prognosis, shorter overall survival, and advanced disease stage 345. In hepatocellular carcinoma, RMI2 acts as a Wnt/β-catenin signaling target that promotes epithelial-mesenchymal transition, cell invasion, and metastasis 3, while in breast cancer it accelerates proliferation and migration via PI3K/AKT pathway activation 4. Pan-cancer analysis reveals RMI2 correlates with tumor mutation burden, microsatellite instability, and immune checkpoint expression 6. These findings position RMI2 as a potential diagnostic and therapeutic target in cancer.