SHLD2 and cancer: Specifically, phosphorylation of the S/T‐Q sites at the N‐terminus of 53BP1 by ATM is required for DNA end protection and immunoglobulin class switch recombination (CSR),[14, 15] promoting its interaction with RIF1, activating NHEJ repair and cancer cell survival.[16, 17] Furthermore, 53BP1 ubiquitylation on K1268 by RNF168 is critical for NHEJ repair, maintaining genomic stability and radiosensitivity.[18, 19, 20] However, the PTMs regulating SHLD2 have not been extensively characterized.