ARPC1B is a regulatory subunit of the Arp2/3 complex, a multiprotein machinery that nucleates branched actin polymerization 12. Beyond its cytoplasmic roles in cell motility and cytoskeletal organization, ARPC1B promotes nuclear actin polymerization to regulate gene transcription and homologous recombination DNA repair, driving motility of double-strand breaks 3. Pathogenic variants in ARPC1B cause Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia, with loss-of-function mutations identified in whole-genome sequencing studies of primary immunodeficiency cohorts 45. Beyond inherited immunodeficiency, ARPC1B is aberrantly expressed in multiple malignancies. In glioblastoma, ARPC1B elevation promotes macrophage-mediated immunosuppression by stabilizing STAT1 and increasing IL10 production, mediating immune checkpoint inhibitor resistance 6. In glioma stem cells, ARPC1B maintains mesenchymal phenotype and radiotherapy resistance by preventing TRIM21-mediated degradation of IFI16 and HuR, activating NF-κB and STAT3 pathways 7. In pancreatic cancer, ARPC1B+ cancer stem cells confer gemcitabine resistance that can be overcome by direct ARPC1B inhibition 8. These findings establish ARPC1B as both a primary immunodeficiency gene and an emerging therapeutic target in cancer.