Abstract:Canonical function of aminoacyl-tRNA synthetase (aaRS) is providing materials for protein biosynthesis. Emerging evidence shows that several aaRS can be secreted as extracellular cytokines， which further regulate cellular and organismal functions， and participate in the etiology of specific diseases. The functional form of secreted aaRS could be divided into three types: the whole molecules， proteolytic fragments and disease-associated mutants. Secreted aaRS could regulate a broad range of target cells including endothelial， immune cells and neuron cells.The ongoing investigations will provide us a more detailed picture of the process of aaRS secretion， their physiological function and potential roles in causing diseases. Herein， the identification of secreted aaRS， their intracellular regulatory mechanisms and pathological implications will be summarized.