RASD2 functions as a GTPase signaling protein, which means it binds to and hydrolyzes GTP. This activity is essential for regulating signaling pathways involving G-protein-coupled receptors and heterotrimeric proteins such as GNB1, GNB2, and GNB3 . The protein is enriched in the striatum, a region of the brain involved in motor control and cognitive functions .
One of the critical roles of RASD2 is its function as an E3 ligase for the attachment of small ubiquitin-like modifier (SUMO) proteins. This modification process, known as sumoylation, is vital for various cellular processes, including nuclear-cytosolic transport, transcriptional regulation, apoptosis, and protein stability .
RASD2 has been implicated in several neurological disorders. For instance, it binds to mutant huntingtin (mHtt), the protein mutated in Huntington’s disease (HD). Sumoylation of mHtt by RASD2 may contribute to the degeneration of the striatum observed in HD patients . Additionally, reduced levels of RASD2 mRNA have been found in HD patients, suggesting a potential role in the disease’s pathology .
Moreover, RASD2 is involved in the activation of the mechanistic target of rapamycin 1 (mTOR1), which plays a role in myelination, axon growth, and regeneration . This function is crucial for maintaining neuronal health and function.