{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRab29, also known as Rab7L1, is emerging as a pivotal regulator of intracellular trafficking pathways linked to Parkinson’s disease. Multiple studies have shown that membrane‐bound, GTP‐loaded Rab29 interacts directly with LRRK2, a major Parkinson’s disease kinase, thereby recruiting it to the trans‐Golgi network. In this context, pathogenic LRRK2 mutations enhance Rab29 phosphorylation—most notably at Ser72—leading to altered Golgi morphology and defective vesicle sorting. These reciprocal interactions suggest that Rab29 functions as a “gatekeeper” that modulates LRRK2 activity and mitigates endolysosomal as well as Golgi trafficking defects implicated in neurodegeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRab29 is also essential for proper vesicular trafficking beyond modulating LRRK2. Experiments in neuronal and non‐neuronal models reveal that Rab29 localizes predominantly to the trans‐Golgi network, where its activity is required to maintain organellar integrity and mediate retrograde trafficking of key cargoes such as the mannose‐6‐phosphate receptor. Furthermore, Rab29 forms molecular partnerships with proteins like C9ORF72 to regulate both intracellular and extracellular vesicle trafficking, and its disruption as well as interference by pathogenic bacterial kinases compromise phagosome–lysosome fusion—a defect that promotes survival of intracellular pathogens."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in the nervous system, Rab29 also contributes to receptor recycling in immune cells. In T lymphocytes, Rab29 coordinates with other Rab proteins and motor complexes to ensure proper recycling of the T-cell antigen receptor to the immune synapse, a process essential for effective immune signaling. Alterations in this recycling pathway suggest that Rab29’s regulatory functions extend to diverse cellular contexts and may impact broader aspects of cell–cell communication."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and expression studies across multiple populations further underscore the relevance of Rab29 in disease. Variants and coding mutations within the PARK16 locus—where Rab29 (Rab7L1) is located—have been associated with altered Parkinson’s disease risk and have been observed in diverse ethnic cohorts, including Ashkenazi Jewish, Asian, and Caucasian populations. In some studies, novel polymorphisms and altered expression levels of Rab29 correlate with disease severity and other pathophysiological features, such as in pituitary adenomas, thereby reinforcing its multifaceted role in human disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "David A MacLeod, Herve Rhinn, Tomoki Kuwahara, et al. 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