However, the roles of RNF126 in promoting or inhibiting the NHEJ or HR repair pathway remain controversial.[18, 19, 20, 21] In this study, we evaluated the role of RNF126 in the DDR regulation in vivo by generating a Rnf126 whole‐body KO mouse model, a PyMT‐induced primary breast cancer model, and a mouse model with TNBC in the brain. This evidence concerns the gene RNF126 and breast carcinoma.