SHLD2 (shieldin complex subunit 2) is a critical component of the four-protein shieldin complex that regulates DNA double-strand break (DSB) repair pathway choice 1. The protein contains three C-terminal oligonucleotide-binding (OB) fold domains that directly bind single-stranded DNA, analogous to RPA1 and POT1 1. SHLD2 functions downstream of 53BP1 and RIF1 to promote non-homologous end joining (NHEJ) by suppressing DNA end resection and preventing homologous recombination 12. Within the shieldin complex, SHLD2 facilitates MAD2L2 (REV7) dimerization, which accelerates MAD2L2-SHLD3 interaction and is essential for proper complex assembly 3. The protein's DNA repair function is regulated by post-translational modifications, as USP25 deubiquitinates SHLD2 at lysine 64, enhancing its binding to REV7 and promoting NHEJ activity 4. SHLD2 mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination and telomere fusion 1. Loss of SHLD2 function causes PARP inhibitor resistance in BRCA1-deficient cancers by restoring homologous recombination capability 12. The protein's overexpression in triple-negative breast cancers correlates with poor patient survival 5.