GTP-binding protein Rheb

RHEB (GTP-binding protein Rheb) is a small GTPase that functions as an allosteric activator of the mTORC1 complex, a central nutrient sensor regulating anabolic reactions and macromolecule biosynthesis (UniProt: Q15382). RHEB responds to nutrients, growth factors, and amino acids by activating the protein kinase activity of mTOR, thereby promoting phosphorylation of downstream effectors including RPS6KB1/2 and EIF4EBP1. The protein is inactivated by the TSC-TBC complex during nutrient starvation to suppress mTORC1 signaling.

RHEB is widely expressed and central to cellular growth pathways. UniProt records no primary disease associations for this gene.

In Alzheimer's disease, RHEB is consistently downregulated in post-mortem AD brain tissue relative to age-matched controls (mean log2FC −0.1047; Chaparral AD proteomics). This reduction was detected across 4 subcellular fractions (P2, P3, S2, S3) in TMT-labeled proteomic analysis. The downregulation of this mTORC1 activator may reflect impaired nutrient sensing or anabolic capacity in AD neurons, consistent with metabolic dysfunction observed in Alzheimer's pathology.