SHLD1, also known as FAM35A, is a key protein in the field of DNA damage repair. As a core component of the Shieldin complex, SHLD1 plays a critical role in maintaining genomic stability. Its primary function is to inhibit the resection of DNA double-strand break ends, directing repair toward the non-homologous end joining pathway while suppressing accurate homologous recombination repair. This function makes SHLD1 an important target for cancer therapy. In BRCA-mutant tumors, the expression level of SHLD1 directly affects the efficacy of PARP inhibitors-intact SHLD1 function renders cancer cells sensitive to the drugs, while its loss leads to drug resistance. Therefore, SHLD1 is not only a fundamental element in basic research on DNA damage response mechanisms but also a highly valuable tumor biomarker and prognostic indicator, offering new directions for personalized cancer treatment.