Description
Rab12 is a member of the RAS oncogene family and plays a crucial role in intracellular membrane trafficking. This small GTPase protein is involved in the transport of vesicles, particularly from recycling endosomes to lysosomes, and is essential for processes like autophagy and the degradation of the transferrin receptor. Rab12 cycles between an inactive GDP-bound form and an active GTP-bound form, recruiting various effectors responsible for vesicle formation, movement, and fusion. In addition to being a substrate for phosphorylation by LRRK2 (Leucine-Rich Repeat Kinase 2), Rab12 has recently been identified as its significant regulator. It has been shown that Rab12 can activate LRRK2, leading to increased phosphorylation of Rab10, another protein involved in intracellular trafficking. This activation is particularly notable in the context of lysosomal damage, where Rab12 helps recruit LRRK2 to lysosomes, enhancing its activity. Dysregulation of this pathway due to pathogenic LRRK2 mutations can contribute to the neurodegenerative processes observed in Parkinson’s disease.