Rabggtb, the β subunit of GGTase II, is a key component in protein prenylation, a post-translational modification. Protein prenylation is involved in membrane association and proper localization of proteins. It also regulates autophagy via Rab7 geranylgeranylation, which is crucial for the degradation of abnormal proteins in cells [1,2].

In the context of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease, overexpression of Rabggtb via lentiviral transfection in NSC34-hSOD1G93A and TDP-43 cells improved cell proliferation by facilitating autophagosome-lysosome fusion. It also reduced the abnormal aggregation of SOD1 protein [1]. In SOD1G93A mice, overexpressing Rabggtb in spinal cord motoneurons via adeno-associated virus delayed the onset time and survival time, decreased SOD1 misfolding and glial overactivation [2]. Additionally, in ALS patients, the level of Rabggtb in monocytes and monocyte-derived macrophages was higher compared to healthy controls, and was significantly correlated with the ALSFRS-R and disease progression levels, suggesting it could be an indicator for tracking ALS progression [3,4].

In summary, Rabggtb is essential for protein prenylation-mediated autophagy. Studies in ALS-related cell and mouse models have revealed its potential therapeutic role in ALS, offering new insights into developing treatment strategies for this devastating neurodegenerative disease.