Recent developments in tRNA sequencing technologies enabled more accurate quantification of tRNA pools in a variety of cells and tissues, showing large differences in expression of distinct tRNAs. Despite our detailed understanding of tRNA biogenesis, there is still no mechanistic evidence on the differential expression of tRNAs. I explore some hypothesis on the control function of two transcription factors mediating transcription of tRNA genes. In parallel, I work on taming various tRNA species to correct mutations (e.g. premature termination, frameshift) linked to devastating human pathologies.