Ras-related protein D2 (RASD2) (RASD2)

Ras-related protein D2 (RASD2), commonly known as Rhes, is a small GTPase that is highly enriched in the striatum of the brain (UniProt P48551). It plays a critical role in the pathogenesis of Huntington's disease (HD) by acting as a SUMO E3 ligase that promotes the sumoylation of mutant huntingtin (mHTT) protein (Subramaniam et al., Science, 2009). This modification increases the solubility and cytotoxicity of mHTT, contributing to the selective neurodegeneration observed in the striatum. Because RASD2 expression is largely restricted to the striatum, it is considered a promising therapeutic target for HD to minimize systemic side effects. Current drug development efforts, such as the antisense oligonucleotide IONIS-RASD2Rx, target RASD2 mRNA for degradation to reduce Rhes protein levels and mitigate mHTT-induced toxicity (Ionis Pharmaceuticals, 2024). Beyond HD, RASD2 is also involved in modulating dopaminergic signaling and has been investigated in the context of Parkinson's disease and other movement disorders (PubMed: 22509270).

Other names

RhesRas homolog enriched in striatumTEM2MGC:4834

Antisense oligonucleotide-mediated degradation of mRNA via RNase H1 recruitment