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The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Zfp335bloto/bloto mice exhibit a naïve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. The effects of Zfp335bloto are multigenic and cannot be attributed to altered thymic selection, proliferation or Bcl2-dependent survival. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function, and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. These findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation. DOI: http://dx.doi.org/10.7554/eLife.03549.001, eLife digest To defend our bodies against a variety of foreign microbes, our immune system makes cells called T cells that can identify these invaders and help to destroy them. There are several types of T cells that play different roles in the immune response: some activate other immune cells, while others destroy cells that have been infected by viruses or other pathogens. T cells develop in a specialized organ called the thymus, where they go through a rigorous selection process before being released as mature T cells into the rest of the body. This selection process includes eliminating individual T cells that are found to be sub-standard, perhaps because they might mistake our own cells for enemy cells. However, many of the details of the later stages of T cell development are not fully understood. Han et al. have now found that a protein called Zfp335 that is involved in the production of mature T cells. Mice carrying a mutation in the gene that makes this protein have fewer mature T cells than normal mice. Han et al. also reveal that Zfp335 is a transcription factor that can control whether or not other genes are expressed as proteins, and further show that one of these proteins, Ankle2, has an important role in the production of mature T cells. A next step in the work is to define exactly how Zfp335 controls the expression of these genes. It will also be important to determine whether mutations in Zfp335 contribute to human T-cell immunodeficiency. DOI: http://dx.doi.org/10.7554/eLife.03549.002