DAXX is an essential, highly conserved protein that is associated with PML nuclear bodies and might function as a transcriptional repressor. Knockout work seems to indicate that it has an anti-apoptotic role; however, a variety of overexpression studies in cultured cells suggest that the protein instead promotes apoptosis. So which is it? Jennifer Michaelson and Philip Leder have settled this question by using RNA interference to knock down DAXX synthesis in the very cell lines used in the overexpression experiments (see p. 345). They demonstrate that apoptosis is increased in DAXX-depleted cells and that transfection of the anti-apoptotic protein Bcl-2 can rescue this phenotype. These findings indicate that DAXX does indeed protect cells from apoptosis, casting significant doubt on the overexpression work. The authors do, however, observe derepression of transcription in the DAXX-depleted cells, confirming that the protein functions as a repressor. Interestingly, they also identify the transcription factors NF-κB and E2F1 as novel DAXX targets. Since both are implicated in control of apoptosis, inhibition of NF-κB- and E2F1-dependent transcription could underlie the anti-apoptotic activity of DAXX.