Chloroplast biogenesis depends on an extensive interplay between the nucleus, cytosol, and chloroplasts, involving regulatory nucleus-encoded chloroplast proteins, as well as nucleocytosolic photoreceptors such as phytochromes (phys) and other extrachloroplastic factors. However, this whole process is only partially understood. Here, we describe the role of VENOSA4 (VEN4) in chloroplast development and acclimation to adverse growth conditions. A 35S:VEN4–eGFP fusion protein localizes to the nucleus in Arabidopsis (Arabidopsis thaliana) protoplasts, and VEN4 homologs are present in a wide range of eukaryotes including humans, where the corresponding homolog (SAMHD1) cleaves dNTPs. Defective photosynthesis in ven4 seedlings results from reduced accumulation of photosynthetic proteins and appears to be caused by a reduction in the translational capacity of chloroplasts. The negative effect of the ven4 mutation on photosynthesis can be phenotypically suppressed by germinating seeds in the presence of excess dCTP or a pool of dNTPs, implying that VEN4, like human SAMHD1, is involved in dNTP catabolism. Moreover, VEN4 activity is also required for optimal responses to cold and salt stresses. In conclusion, our work emphasizes the importance of the nucleocytosolic compartment and the fine-tuning of dNTP levels for chloroplast translation and development.