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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RILPL2
Rab interacting lysosomal protein like 2
Chromosome 12 · 12q24.31
NCBI Gene: 196383Ensembl: ENSG00000150977.12HGNC: HGNC:28787UniProt: A0ABB0MVH7
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolidentical protein bindingprotein bindingepithelial cell morphogenesisneurodegenerative diseasemusculoskeletal system diseasesleep apneaBack pain
✦AI Summary

RILPL2 (Rab interacting lysosomal protein like 2) is an adaptor protein that regulates cellular trafficking and ciliogenesis through interactions with phosphorylated Rab GTPases and the motor protein Myosin Va. RILPL2 binds with high affinity to LRRK2-phosphorylated Rab8A and Rab10 via a specialized X-cap recognition motif involving dual arginine residues (R130 and R132) that interact with phosphorylated threonine residues 1. This interaction redistributes Myosin Va to pericentriolar regions, and RILPL2 overexpression blocks ciliogenesis in retinal pigment epithelium cells 2. In migrating cells, RILPL2 functions as an adaptor protein facilitating Myosin Va-mediated transport of Rab10-CAV1-marked intraluminal vesicles to migrasomes, enabling intercellular communication and wound healing responses 3. Clinically, RILPL2 shows tumor-suppressive functions in breast cancer, where overexpression inhibits proliferation and metastasis via the TUBB3/PTEN pathway and reverses chemoresistance 4. In non-small cell lung cancer, reduced RILPL2 expression correlates with worse overall survival and lower CD4+ and CD8+ T cell infiltration, suggesting RILPL2 regulates tumor immunity 56. RILPL2 has also been identified as a hub gene in fibromyalgia immune-related networks 7.

Sources cited
1
RILPL2 functions as an adaptor protein with Myosin Va in transport of Rab10-CAV1 vesicles to migrasomes during cell migration and wound healing
PMID: 39008679
2
RILPL2 binds LRRK2-phosphorylated Rab10 and Myosin Va, and its overexpression blocks ciliogenesis in RPE cells
PMID: 33727250
3
RILPL2 recognizes phosphorylated Rab GTPases through dual arginine residues (R130 and R132) in its X-cap domain
PMID: 33887226
4
RILPL2 is downregulated in breast cancer; its overexpression inhibits proliferation and metastasis via TUBB3/PTEN pathway and reverses chemoresistance
PMID: 31497344
5
Low RILPL2 expression in NSCLC correlates with worse overall survival and reduced immune cell infiltration
PMID: 36536539
6
RILPL2 expression is significantly positively correlated with CD4+ and CD8+ T cell infiltration in NSCLC tissues
PMID: 39078518
7
RILPL2 is identified as a hub gene in immune-related gene networks associated with fibromyalgia
PMID: 40070065
8
RILPL2 is identified as a candidate disease gene in genetic disease screening studies
PMID: 28600779
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.31Weak
musculoskeletal system diseaseOpen Targets
0.30Weak
sleep apneaOpen Targets
0.30Weak
Back painOpen Targets
0.30Weak
Low back painOpen Targets
0.26Weak
osteoarthritis, kneeOpen Targets
0.26Weak
SciaticaOpen Targets
0.24Weak
osteoarthritis, hipOpen Targets
0.23Weak
non-small cell lung carcinomaOpen Targets
0.09Suggestive
MODYOpen Targets
0.05Suggestive
asthmaOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.04Suggestive
spondyloarthropathyOpen Targets
0.04Suggestive
morbid obesityOpen Targets
0.04Suggestive
lagophthalmosOpen Targets
0.04Suggestive
diabetes mellitus, permanent neonatal 4Open Targets
0.04Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.04Suggestive
hypertriglyceridemia 2Open Targets
0.04Suggestive
lung adenocarcinomaOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MYO5AProtein interaction97%RAB10Protein interaction97%RAB8AProtein interaction83%RAB12Protein interaction80%RAB36Protein interaction73%RAB29Protein interaction72%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
68%
Ovary
25%
Liver
18%
Heart
16%
Brain
13%
Gene Interaction Network
Click a node to explore
RILPL2MYO5ARAB10RAB8ARAB12RAB36RAB29
PROTEIN STRUCTURE
Preparing viewer…
PDB6SQ2 · 1.68 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.51LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.02 [0.70–1.51]
RankingsWhere RILPL2 stands among ~20K protein-coding genes
  • #13,727of 20,598
    Most Researched22
  • #15,212of 17,882
    Most Constrained (LOEUF)1.51
Genes detectedRILPL2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Rab10-CAV1 mediated intraluminal vesicle transport to migrasomes.
PMID: 39008679
Proc Natl Acad Sci U S A · 2024
1.00
2
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet · 2017
0.90
3
Prognostic value of RILPL2 and its correlation with tumor immune microenvironment and glycolysis in non-small cell lung cancer.
PMID: 36536539
Cell Cycle · 2023
0.80
4
LRRK2-phosphorylated Rab10 sequesters Myosin Va with RILPL2 during ciliogenesis blockade.
PMID: 33727250
Life Sci Alliance · 2021
0.70
5
Development of a Novel 11-Gene Signature Related to Immune Subtypes for Fibromyalgia.
PMID: 40070065
Endocr Metab Immune Disord Drug Targets · 2026
0.60