Aminoacyl-tRNA synthetase catalyzing the first reaction of protein biosynthesis. In mammalian cells, eight aminoacyl-tRNA synthetases (aaRSs) and three auxiliary protein factors form a macromolecular aminoacyl-tRNA synthetases complex (aaRS complex). The three nonsynthetase protein factors, namely, p43, p38, and p18 were found to be involved in many other important life activities besides their roles in the complex. The auxiliary factor p43 was the precursor of endothelial monocyte activating polypeptideⅡ(EMAPⅡ), which involved in angiogenesis and apoptosis. The auxiliary factor p38 was crucial for the development of lung, and its abnormal accumulation in neuron would be related to the Parkinson’s disease. The auxiliary factor p38 and p18 could promote the repair of DNA damage via different pathways in a highly organized way. All these breakthroughs enhance our understanding about the interaction between the aaRS complex and the macromolecular signaling network and promote the studies on this field.