The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to 
many cues, such as nutrient status and energy level. Amino acids induce mTORC1 
activation on lysosomes via the small Rag GTPases and the Ragulator complex, 
thereby controlling protein translation and cell growth. Here, we identify the 
human 11-pass transmembrane protein SLC38A9 as a novel component of the 
Rag-Ragulator complex. SLC38A9 localizes with Rag-Ragulator complex components 
on lysosomes and associates with Rag GTPases in an amino acid-sensitive and 
nucleotide binding state-dependent manner. Depletion of SLC38A9 inhibits mTORC1 
activity in the presence of amino acids and in response to amino acid 
replenishment following starvation. Conversely, SLC38A9 overexpression causes 
RHEB (Ras homolog enriched in brain) GTPase-dependent hyperactivation of mTORC1 
and partly sustains mTORC1 activity upon amino acid deprivation. Intriguingly, 
during amino acid starvation mTOR is retained at the lysosome upon SLC38A9 
depletion but fails to be activated. Together, the findings of our study reveal 
SLC38A9 as a Rag-Ragulator complex member transducing amino acid availability to 
mTORC1 activity.