The WASH complex is a regulator of the actin nucleator Arp2/3 and is involved in the trafficking of receptors from the endosome. FAM21, its largest subunit, has a key role in WASH function and also mediates WASH complex assembly. In addition, the long tail of FAM21 has been shown to interact with a number of factors that are involved in receptor trafficking. Zhi-Hui Deng, Daniel Billadeau and co-workers (p. 373) now make use of a FAM21 deletion mutant that does not associate with known interaction partners to identify new binding partners. Surprisingly, they find components of the nuclear factor κB (NF-κB) pathway, including the NF-κB subunits p65 and p50. Furthermore, their data suggest that FAM21 forms new complexes with p65 and p50 independent of the WASH complex and, indeed, depletion of FAM21, but not WASH, decreased the expression of NF-κB target genes. Interestingly, FAM21 depletion sensitises pancreatic cancer cells to chemotherapeutic drugs. The authors also address the molecular mechanism of this new FAM21 function and show that it does not affect the nuclear translocation of NF-κB. Instead, FAM21 interacts with p65 in the nucleus, where it might affect transcriptional activity of the NF-κB pathway at least in part at the level of p65 recruitment to chromatin. Taken together, the data presented here point to a new and unanticipated function of FAM21 in the nucleus – a role it fulfils outside of the WASH complex – that opens new avenues of research, in particular with regard to the possible contribution of FAM21 to cancer cell survival.