Mechanisms controlling apoptosis or cell death in photoreceptor cells are of importance because loss of these cells can result in blindness. Chen and Cepko report that histone deacetylase (HDAC) 4 functions in mouse retina to support survival of retinal neurons. Depletion of HDAC4 increased cell death. Overexpression of HDAC4, on the other hand, supported retinal cell survival. HDACs produce some of their effects by modifying histones associated with DNA, which alters transcription. However, in this case, HDAC4 was predominantly found in the cytoplasm, and mutation of HDAC4 to promote its exclusion from the nucleus did not prevent its protective effects on the retinal cells. Cytoplasmic HDAC4 may act by interacting with the transcription factor hypoxia-inducible factor 1α (HIF1α); deacetylation of HIF1α promotes its stability and accumulation in the nucleus.