Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear hormone receptor that regulates cellular responses through both direct DNA binding and its ability to interact with and sequester proteins such as NF-κB and STAT transcription factors. However, recent evidence indicates that PPARγ is also present in the cytoplasm under some conditions. Andreas von Knethen, Bernhard Brüne and colleagues (p. 192) now characterise a mechanism by which PPARγ subcellular localisation can be regulated in cell lines and primary mouse macrophages. They first show that the phosphorylation of PPARγ at two serine residues by casein kinase II is required for PPARγ export from the nucleus to the cytoplasm. Second, they find that PPARγ export depends on a nuclear export receptor known as CRM1, and that the GTPase Ran and its co-factor RanBP3 are involved. Third, they show that ERK1 activity is also required for PPARγ nuclear export because ERK1 phosphorylation of RanBP3 permits a CRM1-RanBP3 interaction that enhances the binding of CRM1 to its cargo. Given that other mechanisms for PPARγ nuclear export have previously been reported, these data indicate that several different export mechanisms might regulate the cytoplasmic localisation of this protein in a context-dependent manner.