The transcription factors tfeb and tfe3 belong to the MiT/TFE gene family and are known as master regulators of lysosomal function and autophagy. In normal conditions, they are sequestered in the cytosol of the cells and their nuclear translocation is finely regulated in response to a huge array of cell signals; however, the role of these transcription factors during vertebrate development remains unclear. We used zebrafish to investigate tfeb and tfe3 role during embryo development and in adult organs. We generated knock-out (KO) alleles for all the zebrafish tfeb and tfe3s isoforms. Our data show that triple-KO (tfeb-tfe3a-tfe3b) animals are lethal, and these transcription factors are involved in pancreas and liver development. Using the TMT-18plex labeling based quantitative proteomics method and liquid chromatography-tandem mass spectrometry (LC-MS/MS) we performed comparative proteomic analysis of 5 days post fertilization embryos (P1470 files) and adult liver organs (P1408 files) from 2 groups (WT and triple-KO).