In the post genome project era, it is well established that the human genome contains a smaller number of genes than expected. The complexity found in higher organisms can be explained if proteins are multifunctional. Indeed, recent studies are continuing to reveal proteins that are capable of a broad repertoire of functions. A good paradigm for multifunctionality can be found in the amino-acyl tRNA synthetases (aaRSs), an ancient conserved family of proteins. This unique family, which is comprised of 20 different enzymes, is well known for its participation in protein synthesis. Several studies have described numerous examples of these "housekeeping" proteins taking part in extensive critical cellular activities. In this review, we focus on a member of that family, lysyl-tRNA synthetase (LysRS), which has been shown to have a dual functionality. In addition to its contribution to the translation process, LysRS also takes part in the regulation of MITF and USF2 target genes. This phenomenon was first described in mast cells.