mTORC1 (mammalian target of rampamycin complex 1) is a highly conserved protein 
complex regulating cell growth and metabolism via its kinase mTOR (mammalian 
target of rapamycin). The activity of mTOR is under the control of various 
GTPases, of which Rheb and the Rags play a central role. The presence of amino 
acids is a strict requirement for mTORC1 activity. The heterodimeric Rag GTPases 
localize mTORC1 to lysosomes by their amino-acid-dependent interaction with the 
lysosomal Ragulator complex. Rheb is also thought to reside on lysosomes to 
activate mTORC1. Rheb is responsive to growth factors, but, in conjunction with 
PLD1 (phospholipase D1), is also an integral part of the machinery that 
stimulates mTORC1 in response to amino acids. In the present article, we provide 
a brief overview of novel mechanisms by which amino acids affect the function of 
Rags. On the basis of existing literature, we postulate that Rheb is activated 
at the Golgi from where it will travel to lysosomes. Maturation of endosomes 
into lysosomes may be required to assure a continuous supply of GTP-bound Rheb 
for mTORC1 activation, which may help to drive the maturation process.