Lysyl-tRNA synthetases are synthesized from two distinct genes in Escherichia coli, lysS (constitutively) and lysU (inducibly); however, the physiological significance and the differential control mechanism of these two genes have been a long-standing puzzle. Recent studies have successfully uncovered a significant control mechanism of lysU expression, which involves the leucine-responsive regulatory protein (Lrp) and a translational enhancer element called 'downstream box'. Moreover, it is likely that there is a mechanism underlying co-ordinate expression of lysU with other genes outside the leucine-Lrp regulon under harsh conditions such as low pH and anaerobiosis. A possible mechanism of lysyl-tRNA synthetase expression and function is reviewed.