Leucyl-tRNA synthetase (LRS) is a class I enzyme, with Rossman fold, a large-insertion CP1 domain, a tRNA-binding anticodon domain, and a C-terminal extension domain. In higher eukaryotes, LRS is a component of the multi-tRNA synthetase complex (MSC), which consists of nine tRNA synthetases and three nonenzymatic components. The C-terminal domain of LRS is crucial for its interaction with other components of MSC. Several different components are involved in various cell-signaling processes, such as rRNA biogenesis and antiapoptotic signal regulation.

In the presence of amino acids, LRS translocates to the lysosome, where it interacts with and facilitates GTP hydrolysis of RagD, which is required for mTORC1 activation. LRS functionally regulates autophagy through mTORC1 regulation. LRS is an important regulator of the mTORC1-autophagy regulatory circuit. Induction of autophagy by amino acid deprivation is required to maintain amino acid homeostasis and protein synthesis. LRS may sense increased leucine and activates mTORC1 via RagD GTPase in order to suppress autophagy.[1]