ACTR2 (actin-related protein 2) is an ATP-binding core component of the Arp2/3 complex, a multiprotein machine that nucleates branched actin filaments in response to nucleation-promoting factors. In the cytoplasm, the Arp2/3 complex generates the force for cell motility and lamellipodium formation; in podocytes, ACTR2 is required for lamellipodia assembly downstream of AVIL and PLCE1 signaling. Beyond cytoskeletal functions, ACTR2 participates in nuclear actin polymerization, where it supports gene transcription and homologous recombination repair of DNA damage by promoting double-strand break mobility. Additionally, ACTR2 preserves nuclear envelope integrity as part of the peri-nuclear actin cap, a role linked to suppression of cellular senescence 1. Recent studies associate ACTR2 with diverse pathological states: genome-wide analyses identify ACTR2 variants at the 2p14 locus as protective against rheumatoid arthritis through feedback regulation with SPRED2 in synovial fibroblasts 2, and differential ACTR2 expression correlates with recurrent pregnancy loss and calcific aortic stenosis 34. In oocyte meiosis, ACTR2 is required for proper spindle assembly and migration 5, and in renal fibrosis, a circular RNA derived from ACTR2 promotes pathological M2 macrophage polarization 6. These findings position ACTR2 as a multifunctional regulator relevant to immunological, cardiovascular, reproductive, and fibrotic disease.