ARPC3 is a core structural component of the Arp2/3 complex, a multiprotein machinery essential for actin filament nucleation and branching 1. The complex mediates branched actin network formation in the cytoplasm, providing force for cell motility, and also localizes to the nucleus where it regulates gene transcription and DNA repair 2. Nuclear Arp2/3 complex promotes homologous recombination by facilitating actin polymerization that drives double-strand break motility 2. ARPC3 activation requires nucleation-promoting factors like SPIN90, which dimerizes to engage the Arp2/3 clamp and ARPC3 interface, inducing conformational changes necessary for actin nucleation 3. Clinically, ARPC3 associations span multiple pathologies: rare disease analysis identified ARPC3 variants linked to Charcot-Marie-Tooth disease 4, while dysregulated ARPC3 expression correlates with cancer progression. In breast cancer, elevated ARPC3 promotes metastatic potential through F-actin reorganization and epithelial-mesenchymal transition, though therapeutic inhibition reduces metastasis 5. ARPC3 has been identified as a diagnostic biomarker in osteosarcoma 6 and chr12 obstructive pulmonary disease 7. A CpG-SNP in the ARPC3 promoter associates with hypertriglyceridemia in obese patients 8, highlighting metabolic regulatory functions beyond cytoskeletal control.