protein
ADP-ribosylation factor-like protein 8B
Gene
ARL8B
Organism
Homo sapiens(9606)
Length
186 aa
Mass
21,539 Da
ARL8B (ADP-ribosylation factor-like protein 8B) is a small GTPase that functions as a molecular switch cycling between active GTP-bound and inactive GDP-bound states (UniProt: Q9NVJ2). It localizes to lysosomal membranes and orchestrates lysosomal positioning, transport, and fusion by recruiting effector proteins including PLEKHM2 and the kinesin-1 motor complex. The protein plays critical roles in lysosomal exocytosis, anterograde axonal transport of presynaptic vesicles, endosome-to-lysosome trafficking, and antigen presentation pathways.
In neurons, ARL8B mediates long-range anterograde transport of lysosome-related vesicles essential for presynaptic biogenesis and synaptic function (UniProt: Q9NVJ2). The protein regulates cargo delivery to lysosomes through interaction with PLEKHM1 and assembly of the HOPS complex, directing antigen-lysosome intersection and phagolysosome formation for microbial killing. Beyond immune functions, ARL8B may influence chromosome segregation and has been implicated in unconventional egress pathways during viral infection.
ARL8B is downregulated in Alzheimer's disease brain tissue relative to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.40 across post-mortem human AD brain subcellular fractions. This reduction may compromise lysosomal dynamics and axonal transport, processes increasingly recognized as disrupted in neurodegeneration.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.400
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.3997 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Small GTPase which cycles between active GTP-bound and inactive GDP-bound states (PubMed:15331635, PubMed:16537643). In its active state, binds to a variety of effector proteins playing a key role in the regulation of lysosomal positioning which is important for nutrient sensing, natural killer cell-mediated cytotoxicity and antigen presentation. Along with its effectors, orchestrates lysosomal transport and fusion (PubMed:16537643, PubMed:16650381, PubMed:25898167, PubMed:27808481, PubMed:28325809). Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility by recruiting PLEKHM2, which in turn recruits the motor protein kinesin-1 on lysosomes. Required for lysosomal and cytolytic granule exocytosis (PubMed:22172677, PubMed:24088571, PubMed:29592961). Critical factor involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571). In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function (By similarity). Also acts as a regulator of endosome to lysosome trafficking pathways of special significance for host defense (PubMed:21802320). Recruits RUFY1 onto early endosomes regulating endosomes to trans-Golgi network proteins retrieval (PubMed:36282215). Regulates cargo trafficking to lysosomes by binding to PLEKHM1 and recruiting the HOPS subunit VPS41, resulting in functional assembly of the HOPS complex on lysosomal membranes (PubMed:16537643, PubMed:25908847). Plays an important role in cargo delivery to lysosomes for antigen presentation and microbial killing. Directs the intersection of CD1d with lipid antigens in lysosomes, and plays a role in intersecting phagosomes with lysosomes to generate phagolysosomes that kill microbes (PubMed:21802320, PubMed:25908847). Involved in the process of MHC II presentation. Regulates the delivery of antigens to lysosomes and the formation of MHC II-peptide complexes through the recruitment of the HOPS complex to lysosomes allowing the fusion of late endosomes to lysosomes (By similarity). May play a role in chromosome segregation (PubMed:15331635)
(Microbial infection) During Mycobacterium tuberculosis (Mtb) infection, is required for plasma membrane repair by controlling the exocytosis of lysosomes in macrophages. ARL8B secretion pathway is crucial to control the type of cell death of the M.tuberculosis-infected macrophages, distinguishing avirulent from virulent Mtb induced necrotic cell death
(Microbial infection) During infection, coronaviruses such as SARS-CoV-2 and the chaperone HSPA5/GRP78 are probably co-released through ARL8B-dependent lysosomal exocytic pathway for unconventional egress
Sources
Last updated 5/8/2026, 6:29:57 AM