Alien has characteristics of a corepressor for selected members of the nuclear hormone receptor (NHR) superfamily and also for transcription factors involved in cell cycle regulation and DNA repair. Alien mediates gene silencing and represses the transactivation of specific NHRs and other transcription factors to modulate hormone response and cell proliferation. Alien is a highly conserved protein and is expressed in a wide variety of tissues. Knockout of the gene encoding Alien in mice is embryonic lethal at a very early stage, indicating an important evolutionary role in multicellular organisms. From a mechanistic perspective, the corepressor function of Alien is in part mediated by histone deacetylase (HDAC) activity. In addition, Alien seems to modulate nucleosome assembly activity. This suggests that Alien is acting on chromatin not only through recruitment of histone-modifying activities, but also through enhancing nucleosome assembly.