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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RILP
Rab interacting lysosomal protein
Chromosome 17 · 17p13.3
NCBI Gene: 83547Ensembl: ENSG00000167705.13HGNC: HGNC:30266UniProt: Q96NA2
61PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
lysosomeendosome membranesmall GTPase bindingprotein-containing complexneurodegenerative diseasebreast cancerosteosarcomaneoplasm
✦AI Summary

RILP (Rab interacting lysosomal protein) is a Rab7 effector protein that plays crucial roles in endolysosomal trafficking and cellular homeostasis. RILP regulates lysosomal positioning by recruiting dynein-dynactin motor complexes to Rab7-containing late endosomes and lysosomes, promoting their retrograde transport to perinuclear regions 1. This positioning is functionally significant, as RILP-mediated lysosomal clustering enhances LRRK2-dependent Rab10 phosphorylation in the perinuclear area 1. RILP modulates cholesterol homeostasis by competitively inhibiting VAP-ORP1L interactions, thereby blocking cholesterol transport from endolysosomes to the endoplasmic reticulum and inducing cholesterol accumulation in lysosomes, which triggers autophagy 2. The protein also responds to pH changes, with V-ATPase assembly promoting RILP-mediated Rab7 stabilization during late endosomal pH neutralization 3. Structurally, RILP forms homodimers that interact with single Rab12 molecules through its Rab homology domain 4. In disease contexts, RILP exhibits tumor suppressor activity in osteosarcoma by inhibiting the PI3K/AKT/mTOR pathway through Grb10-mediated mechanisms, suppressing cell proliferation and metastasis while promoting autophagy 5. RILP's multifaceted roles in organelle positioning, cholesterol trafficking, and autophagy regulation make it a critical component of cellular homeostasis.

Sources cited
1
RILP promotes lysosomal clustering in perinuclear regions and enhances LRRK2-dependent Rab10 phosphorylation
PMID: 36256825
2
RILP inhibits VAP-ORP1L interactions, blocks cholesterol transport from endolysosomes to ER, and induces cholesterol accumulation that triggers autophagy
PMID: 39195203
3
RILP responds to pH neutralization through V-ATPase assembly and mediates Rab7 stabilization
PMID: 38578235
4
RILP forms homodimers that interact with Rab12 through its Rab homology domain
PMID: 33986343
5
RILP acts as tumor suppressor in osteosarcoma by inhibiting PI3K/AKT/mTOR pathway through Grb10-mediated mechanisms
PMID: 37789274
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.32Weak
breast cancerOpen Targets
0.08Suggestive
osteosarcomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.05Suggestive
lung cancerOpen Targets
0.03Suggestive
non-small cell lung carcinomaOpen Targets
0.03Suggestive
Abnormality of the skeletal systemOpen Targets
0.02Suggestive
brain aneurysmOpen Targets
0.02Suggestive
rhabdomyolysisOpen Targets
0.02Suggestive
carcinomaOpen Targets
0.02Suggestive
cystinosisOpen Targets
0.02Suggestive
prostate cancerOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
LeishmaniasisOpen Targets
0.01Suggestive
lung carcinomaOpen Targets
0.01Suggestive
diabetic cardiomyopathyOpen Targets
0.01Suggestive
neuronal ceroid lipofuscinosisOpen Targets
0.01Suggestive
non-alcoholic steatohepatitisOpen Targets
0.01Suggestive
ovarian cancerOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DCTN1Protein interaction99%RAB34Protein interaction93%DYNC1H1Protein interaction87%DYNC1I1Protein interaction87%DYNC1I2Protein interaction87%DYNC1LI2Protein interaction87%
Tissue Expression6 tissues
Liver
100%
Heart
95%
Lung
62%
Bone Marrow
43%
Brain
16%
Ovary
10%
Gene Interaction Network
Click a node to explore
RILPDCTN1RAB34DYNC1H1DYNC1I1DYNC1I2DYNC1LI2
PROTEIN STRUCTURE
Preparing viewer…
PDB1YHN · 3.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.98LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.86 [1.45–1.98]
RankingsWhere RILP stands among ~20K protein-coding genes
  • #7,603of 20,598
    Most Researched61
  • #17,811of 17,882
    Most Constrained (LOEUF)1.98
Genes detectedRILP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
ATM loss disrupts the autophagy-lysosomal pathway.
PMID: 32757690
Autophagy · 2021
1.00
2
USP4 depletion-driven RAB7A ubiquitylation impairs autophagosome-lysosome fusion and aggravates periodontitis.
PMID: 39663592
Autophagy · 2025
0.90
3
Cholesterol-rich lysosomes induced by respiratory syncytial virus promote viral replication by blocking autophagy flux.
PMID: 39060258
Nat Commun · 2024
0.80
4
RILP Induces Cholesterol Accumulation in Lysosomes by Inhibiting Endoplasmic Reticulum-Endolysosome Interactions.
PMID: 39195203
Cells · 2024
0.70
5
Lysosomal positioning regulates Rab10 phosphorylation at LRRK2
PMID: 36256825
Proc Natl Acad Sci U S A · 2022
0.60