SHLD1 is a critical component of the shieldin complex, which plays a pivotal role in DNA double-strand break (DSB) repair pathway choice. The shieldin complex, consisting of SHLD1, SHLD2 (FAM35A), SHLD3, and REV7 (MAD2L2), functions downstream of 53BP1 and RIF1 to promote non-homologous end joining (NHEJ) while suppressing homologous recombination 12. SHLD1 mediates this function by helping to restrict DNA end resection and protecting DNA termini from nucleolytic processing 1. The complex localizes to DSB sites in a 53BP1- and RIF1-dependent manner, with SHLD2 directly binding single-stranded DNA through its OB-fold domains 1. SHLD1 expression is tightly regulated by transcription factors THAP1, YY1, and HCF1, maintaining low basal levels essential for proper DSB repair balance 3. Functionally, SHLD1 promotes immunoglobulin class-switch recombination and facilitates telomere fusion processes 1. The complex acts through recruitment of CST-Polα-primase for fill-in synthesis at DNA breaks 45. Clinically, SHLD1 deficiency confers resistance to PARP inhibitors in BRCA1-deficient cancers by restoring homologous recombination capability 26, making it a potential biomarker for treatment stratification.