Ras-related GTP-binding protein C

RRAGC (Ras-related GTP-binding protein C) is a guanine nucleotide-binding protein that regulates cellular responses to amino acid availability through control of the mTORC1 signaling cascade (UniProt: Q9HB90). It functions as part of a heterodimeric Rag complex with RagA or RagB, cycling between inactive GTP-bound and active GDP-bound states to recruit mTORC1 to lysosomes and facilitate its activation by RHEB. The protein also participates in non-canonical mTORC1 signaling that phosphorylates MiT/TFE transcription factors. RRAGC is associated with Long-Olsen-Distelmaier syndrome (LNGODS), an autosomal dominant condition presenting with dilated cardiomyopathy, cataracts, and neurological abnormalities (UniProt: Q9HB90).

In Alzheimer's disease, RRAGC shows reduced abundance in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.41 across analyzed subcellular fractions. This downregulation may impair amino acid-sensing capacity and mTORC1 signaling efficiency, potentially affecting protein synthesis and cellular metabolic homeostasis in affected neurons. The decrease aligns with broader dysregulation of nutrient-sensing pathways observed in AD pathogenesis.