Actin nucleation, the formation of new actin filaments from existing filaments, affects actin filament structure during cell motility, division and intracellular trafficking. An important actin nucleation protein complex is the highly conserved ARP2/3 complex, consisting of ARP2, ARP3 and ARPC1-5. The ARP2/3 complex promotes branching of an existing actin filament and formation of a daughter filament following activation by nucleation-promoting factors, such as WASP/WAVE or cortactin (1). The formation of podosomes, small cellular projections that degrade the extracellular matrix, is enhanced by ARP2/3 complex action. ARP2/3 competes with caldesmon, an actin binding protein shown to negatively affect podosome formation (2). The ARP2/3 complex (along with N-WASP) regulates nuclear actin filament nucleation and controls actin polymerization during transcription (3).