The Arp2/3 complex is essential for the generation of branched actin networks which are involved in many fundamental cellular processes that are essential for life.  The Arp2/3 complex, consists of 7 evolutionary conserved subunits (Arp2, Arp3 and ARPC1-5).  However, in mammals, Arp3, ARPC1 and ARPC5 exist as two different isoforms (Arp3/Arp3B, ARPC1A/ARPC1B and ARPC5/ARPC5L) that are 91, 67 and 67% identical, respectively.  These different subunit isoforms, mean that in humans the Arp2/3 complex is a group of eight iso-complexes.  Previous work from my lab and others has demonstrated that Arp2/3 iso-complexes have different properties and cellular functions.   The importance of Arp2/3 iso-complexes in cell and tissue homeostasis is underscored by the observation that loss of function mutations in human ARPC1B lead to severe inflammation and immunodeficiency.  We have also recently reported that loss of human ARPC5 expression results in multiple congenital anomalies, recurrent infections, systemic inflammation, and mortality.  In my talk I will discuss our ongoing cell and biochemical analysis of Arp2/3 iso-complexes together with unpublished work in mice on their role in immune and neuronal homeostasis.