Table 1.

Rab GTPases and their known localisations and functions under physiological conditions are summarised here, including their various links with Parkinson’s Disease (PD), Huntington’s Disease (HD), Dementia with Lewy Bodies (DLB), and Alzheimer’s Disease (AD). Endoplasmic reticulum (ER), trans-Golgi network (TGN), endoplasmic reticulum Golgi intermediate compartment (ERGIC), amyloid beta (Aß), amyloid precursor protein (APP), cerebral spinal fluid (CSF), knockdown (KD), huntingtin (Htt), leucine-rich repeat kinase 2 (LRRK), neurofibrillary tangles (NFT), Htt-associated protein 40 (HAP40).

Rab GTPase	Localisation	Function	Link with Neurodegenerative Diseases	Citations
Rab1A/B	ER Golgi	Biosynthesis Protein transport Autophagy Cell signalling Migration and proliferation	PD Impaired by α-synuclein Overexpression rescues defects AD Involved in Aß production	[17,18,21,22,23,24,25,26]
Rab2A	ER ERGIC Golgi Autolysosome	Protein anterograde and retrograde transport Autophagy and lysosomal degradation	HD Huntingtin suppression increases Rab2+ vesicle transport	[27,28,29,30,31]
Rab3A/B	Secretory vesicles	Exocytosis	PD α-synuclein interaction Overexpression rescues and protects against dopaminergic neuron loss DLB Rab3 levels decreased in Lewy body dementia—correlates with cognitive decline HD Overexpression rescues impaired vesicle docking and reduces reactive astrocytes AD Regulates Aß production Downregulated in AD brains Involved in APP transport Increased in AD CSF	[24,32,33,34,35,36,37,38,39,40,41]
Rab4A	Early endosome	Protein sorting to both recycling and degradative pathways	AD Upregulated HD Involved in Htt axonal trafficking—disrupted in HD Overexpression rescues synaptic defects, lifespan, and locomotor defects	[42,43,44,45,46]
Rab5	Early endosome Plasma membrane	Early endosome regulation	AD Upregulated and causes enlarged endosomes—early AD pathology Increases Aß production HD Interacts with Htt via HAP40 Modifies mutant Htt toxicity and aggregation	[27,44,45,47,48,49,50,51,52,53,54]
Rab6A	Golgi	Targeting of secretory vesicles during exocytosis	AD Upregulated Interaction with presenilin 1 Dominant negative mutant decreases Aß levels	[55,56,57,58,59]
Rab7	Late endosome Lysosome Phagosomes	Late endosome regulation Lysosome biogenesis Phagosome maturation Autophagy	PD Increases autophagy, reduces cell death, and rescues locomotor deficits HD Reduced Htt impaired Rab7+ vesicle motility AD Upregulated Overexpression decreases tau secretion	[27,31,44,45,49,51,60,61,62,63,64,65]
Rab8	Plasma membrane Synaptic vesicles Autophagosomes	Polarised membrane trafficking Cell morphogenesis Autophagy	PD Overexpression rescues dopaminergic neuron loss Increases α-synuclein aggregation—reduces toxicity Mediates transport of α-synuclein extracellular vesicles HD Rescues HD defects and reduces neurodegeneration Promotes HTT aggregation	[24,66,67,68,69,70,71,72]
Rab10	ER Endosomes Phagosomes GLUT4 vesicles	ER dynamics Endocytosis Phagosome maturation GLUT4 translocation	AD Upregulated in AD brains KD decreases Aß production Phosphorylated Rab10 present in NFTs	[73,74,75,76,77,78]
Rab11A/B	Golgi Recycling endosome	Transport through recycling endosomes Exocytosis	PD Overexpression rescues dopaminergic neuron loss and behavioural deficits HD Impaired activity in HD HTT regulates apical vesicle trafficking of PAR3-aPKC via Rab11A Rab11 dysfunction in HD leads to impaired GLUT3 trafficking contributing to glucose hypometabolism Overexpression rescues neurodegeneration locomotor defects and synaptic changes in HD Overexpression rescues synaptic vesicle defects Dominant active Rab11 normalises cysteine uptake, subsequently increasing glutathione synthesis, clearing ROS, and improving neuronal survival in HD neurons Dominant active Rab11 protects HD neurons from glutamate induced death AD Interacts with presenilins Involved in Aß trafficking	[19,20,79,80,81,82,83,84,85,86,87,88,89,90]
Rab13	TGN Recycling endosomes Plasma membrane	Tight junction maintenance and formation TGN and recycling endosome trafficking	PD Overexpression reduces α-synuclein toxicity	[91,92,93]
Rab19	Golgi	Unknown	HD Reduced Htt perturbs Rab19+ vesicle trafficking	[31,94]
Rab27b	Secretory vesicles Plasma membrane	Secretion and exocytosis regulation	PD Increases α-synuclein clearance via autophagy, decreasing toxicity AD Upregulated	[45,95,96,97]
Rab29	TGN Golgi	TGN maintenance and retrograde trafficking	PD Recruits and stimulates LRRK2	[98,99,100]
Rab31	TGN Golgi Endosomes	TGN vesicle formation and trafficking to the endosomes TGN to plasma membrane trafficking EGFR trafficking to late endosomes	PD Mediates transport of α-synuclein extracellular vesicles	[71,101,102,103,104]
Rab32	ER Mitochondria	Autophagic vacuole formation in autophagy Phagosome maturation Mitochondrial dynamics	PD Regulation of LRRK2	[62,105,106,107,108]
Rab35	Plasma membrane	Endocytic recycling	AD Involved in tau degradative pathway	[109,110,111]
Rab39B	Golgi Early endosome	ER to Golgi GluA2 AMPAR subunit trafficking Synapse formation and maintenance Autophagy	PD Loss of function Rab39B linked to early onset PD, and causes α-synuclein dysregulation AD Sequestered into Aß plaques	[69,112,113,114,115]