Sodium-coupled neutral amino acid transporter 9 (SLC38A9) is a lysosomal amino acid transporter, involved in the regulation of mechanistic target of rapamycin complex 1 (mTORC1) activity in response to amino acid levels within the lysosomal lumen^1,2. A sodium-couple amino acid transporter at the lysosome, SLC38A9, senses arginine from within the lysosome to convey arginine sufficiency to mTORC1.

SLC38A9 forms a complex with other lysosomal resident proteins including the v-ATPase and a pentameric complex called Ragulator^3-5. v-ATPase function is necessary for mTORC1 activation, but the molecular mechanism of this regulation is currently unclear². Ragulator binds strongly to the Rag GTPases and was shown to function as a guanine exchange factor (GEF) for RagA/B^6,7. Potentially SLC38A9 and the v-ATPase are able to regulate mTORC1 activity by modulating Ragulator’s GEF activity. RagA/B is not the only Rag GTPase that is regulated, but a Folliculin-FNIP2 complex is a GAP for RagC/D^8,9.

In short, SLC38A9 is a functional component of the lysosomal amino acid sensing machinery involved in the control of mTORC1 activity, that underlies the regulation of the metabolic status and cellular responses to growth factors, energy, glucose and amino acid levels ⁴.