Abstract Lysyl tRNA synthetase (LysRS) is an aminoacyl-tRNA synthetase (AaRS). This group of ancient proteins, known for their critical role in translation, was found in recent years to function in a variety of other roles. Besides its enzymatic activity in aminoacylation of tRNA, LysRS can produce dinucleotide diadenosine tetraphosphate (Ap4A). Intracellularly, it is found mainly in the cytoplasm as a part of a multisynthetase complex where it interacts with several proteins, most notably AIMP2. Besides its role in translation it has been demonstrated that LysRS can act as a cytokine-like molecule, secreted by cells and having distinct effects on macrophages. Moreover, LysRS can bind to the transcription factors USF2 and MITF and can influence their transcriptional activities following immunological stimulation of mast cells. In this review, we focus on the nontranslational functions of LysRS related to the immune system. We begin with a short discussion of “gene sharing,” proceed to a description of its structural and enzymatic function and then describe some of the in vivo functions of this enzyme.