The Arp2/3 complex is responsible for the assembly of branched actin filaments. Although its cellular functions are well understood, less is known about the consequence of its disruption in developing animals. To investigate the function of Arp2/3 in the skin, Metello Innocenti and colleagues (p. 4588) have generated mice specifically lacking Arpc4, a core component of the complex, in the epidermis (referred to as Arpc4 eKO). These animals developed progressive psoriasis-like lesions soon after birth, accompanied by characteristic dermal inflammation. Differential gene expression analyses reveal upregulation of inflammatory and dermatological disease-related pathways in the affected Arpc4 eKO tissue. The mutant mice show increased epidermal levels and activity of Nrf2, a master regulator of epidermal homeostasis, the hyperactivation of which was previously found to result in severe keratinocyte abnormalities similar to those observed in the Arpc4 eKO. Furthermore, the authors show that Nrf2 interacts with the actin cytoskeleton, and a functional Arp2/3 complex sequesters Nrf2 to the cytoskeleton, effectively blocking its pro-psoriatic transcription factor activity. Intriguingly, Arpc4 appears to be downregulated in human psoriatic lesions and chemically induced psoriasis-like lesions in mice, thus providing further support to the authors’ model whereby loss of Arp2/3 is involved in the pathogenesis of psoriasis.