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SESTRINs regulate mTORC1 via RRAGs: The riddle of GATOR

SESTRINs, proteins encoded by the SESN1–3 genes in mammals, are well-established suppressors of the mechanistic target of rapamycin complex 1 (mTORC1) kinase. Recently, we found that SESTRINs bind the GATOR2 protein complex, which is a regulator of RRAGA/B guanosine triphosphatase. Three independent studies support the RRAGA/B-dependence of mTORC1 regulation by SESTRINs; however, the role of GATOR2 in this process requires clarification.