gene

LRRK2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about LRRK2: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

2625Connections

12Hypotheses

8Analyses

50Outgoing

50Incoming

2Experiments

9Debates

Summary

A gene referenced in 1 knowledge graph relationship. Key connections: inhibits GCase_trafficking (mechanism).

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🧬 Gene Info

Gene Symbol	LRRK2
Full Name	Leucine Rich Repeat Kinase 2
Chromosome	12q12
Protein Type	Protein
Subcellular Localization	Cytoplasmic vesicle, Perikaryon, Golgi apparatus membrane, Cell projection, axon, Cell projection, dendrite, Endoplasmic
Amino Acids	2527 aa
Pathways	MAPK
UniProt ID	Search UniProt
GeneCards	LRRK2
Human Protein Atlas	LRRK2
Associated Diseases	Aging, Als, Alzheimer, Alzheimer's disease, Amyotrophic Lateral Sclerosis
Known Drugs/Compounds	BIIB094, BIIB122, Cigarette Smoking, DNL201, Environmental Toxicants, levodopa
Interactions	6-OHDA, ACETYLCHOLINE, ACHE, Actin, AD, AKT
SciDEX Hypotheses	LRRK2 G2019S Kinase Inhibition for Parkinson's Dis G2019S primarily raises baseline LRRK2 kinase acti Therapeutic Window Exists Because Amplified Signal (+6 more)
KG Connections	2622 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — LRRK2 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

6VP6 — X-ray / Cryo-EM

🔮 AI Predicted Structure

Q5S007 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    LRRK2["LRRK2"] -->|"causes"| PD["PD"]
    LRRK2["LRRK2"] -->|"associated"| Parkinson_s_disease["Parkinson's disease"]
    LRRK2["LRRK2"] -->|"regulates"| SNCA["SNCA"]
    LRRK2["LRRK2"] -->|"causes"| Parkinson_s_disease_1["Parkinson's disease"]
    LRRK2["LRRK2"] -.->|"inhibits"| Parkinson["Parkinson"]
    LRRK2["LRRK2"] -->|"implicated in"| Parkinson_2["Parkinson"]
    GABARAP["GABARAP"] -->|"binds"| LRRK2["LRRK2"]
    STING["STING"] -->|"activates"| LRRK2["LRRK2"]
    CASM_pathway["CASM pathway"] -->|"activates"| LRRK2["LRRK2"]
    GABARAP_3["GABARAP"] -->|"regulates"| LRRK2["LRRK2"]
    style LRRK2 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1699)

Target	Relation	Type	Str
LRRK2	encodes	protein	0.00
PARKINSON	associated_with	gene	1.00
Parkinson	associated_with	disease	1.00
PARKINSON'S DISEASE	associated_with	disease	1.00
Parkinson	causes	disease	1.00
PARKIN	associated_with	gene	0.98
Familial Parkinson'S Disease	associated_with	disease	0.95
RAB	interacts_with	protein	0.95
Parkinson'S Disease	therapeutic_target	disease	0.95
Autophagy Process	regulates	process	0.95
Parkinson Disease	causes	disease	0.95
Mitochondrial Protection	inhibits	process	0.95
Parkinson Disease	risk_factor_for	disease	0.95
Parkinson's Disease	associated_with	disease	0.95
Parkinson'S Disease	causes	disease	0.95
Macroautophagy	regulates	process	0.95
Als	associated_with	disease	0.95
Parkinson	therapeutic_target	disease	0.95
Parkinson's Disease	causes	disease	0.95
Rab GTPases	phosphorylates	protein	0.92
G2019S LRRK2	associated_with	protein	0.90
oxidative stress response	participates_in	pathway	0.90
MLi-2	targets	drug	0.90
G2019S mutation	associated_with	compound	0.90
MEK	activates	protein	0.90
NRF2	regulates	protein	0.90
Α-SYNUCLEIN	associated_with	protein	0.90
NFE2L2	inhibits	gene	0.90
Paneth Cell Dysfunction	causes	phenotype	0.90
Type I Interferon Signaling	modulates	pathway	0.90
Parkinson's disease	regulates	disease	0.90
Crohn's Disease	risk_factor_for	disease	0.90
Chaperone-Mediated Autophagy	modulates	pathway	0.90
PARKINSON DISEASE	associated_with	disease	0.90
Serine 1292 Autophosphorylation	phosphorylates	biomarker	0.90
RAB8A	phosphorylates	protein	0.90
Kinase Activation	involved_in	mechanism	0.90
Autophagy Pathway	involved_in	pathway	0.90
Autophagy-Lysosomal Pathway	regulates	pathway	0.90
autophosphorylation	upregulates	process	0.90
Monocytes	expressed_in	cell_type	0.90
RAB GTPASES	phosphorylates	protein	0.90
Sporadic Parkinson'S Disease	implicated_in	disease	0.90
α-Synuclein Oligomer Accumulation	associated_with	process	0.90
Lysosomal stress	associated_with	process	0.90
PINK1/parkin-mediated mitophagy	inhibits	pathway	0.90
Parkinson's disease	activates	disease	0.90
RAB12 phosphorylation	regulates	phenotype	0.90
RAB10 phosphorylation	regulates	phenotype	0.90
RAB PROTEINS	targets	protein	0.90

Incoming (926)

Source	Relation	Type	Str
entities-snx5	associated_with	wiki	0.00
entities-histone-modifications	interacts_with	wiki	0.00
LRRK2	encodes	gene	0.00
RAB29	recruits	protein	1.00
RAB29	reduces endogenous	protein	1.00
RAB29	operates in a common pathway with	protein	1.00
PARKINSON'S DISEASE	associated_with	gene	1.00
GABARAP	binds	gene	0.95
LRRK2 kinase inhibitors	inhibits	drug	0.95
G2019S	associated_with	biomarker	0.95
BIIB094	targets	drug	0.95
LRRK2 Inhibitors	inhibits	drug	0.95
INTERFERON GAMMA	upregulates	protein	0.90
RAB	activates	protein	0.90
RAB29	regulates	protein	0.90
CASM pathway	activates	pathway	0.90
STING	activates	protein	0.90
MLi-2	inhibits	drug	0.90
PF-06447475	inhibits	drug	0.90
Alternative Polyadenylation	modulates	process	0.90
PARKINSON'S DISEASE	therapeutic_target	gene	0.90
ALZHEIMER'S DISEASE	associated_with	disease	0.88
PPM1H	inhibits	protein	0.88
RAB29	recruits_to_TGN	gene	0.85
PRKN	interacts_with	gene	0.85
VPS35	associated_with	protein	0.85
PINK1	epistasis_with	gene	0.85
Endolysosomal Dysfunction	activates	process	0.85
PIKFYVE	regulates	protein	0.85
Oxidative Stress	activates	process	0.85
CRISPR-Cas9	targets	process	0.85
IFN	interacts_with	gene	0.80
GCASE	interacts_with	protein	0.80
MIRO1	interacts_with	protein	0.80
Chaperone Network	regulates	pathway	0.80
Environmental Toxicants	activates	compound	0.80
lysosome damage	activates	phenotype	0.80
EEF2	phosphorylates	gene	0.80
GABARAP	regulates	protein	0.80
PINK1	associated_with	gene	0.80
NEURODEGENERATION	associated_with	gene	0.80
Cigarette Smoking	activates	compound	0.75
LAMP1	activates	gene	0.70
GSK3B	activates	gene	0.70
FOXP3	activates	gene	0.70
ACHE	activates	gene	0.70
ATP13A2	expressed_in	gene	0.70
ACHE	targets	gene	0.70
ASTROCYTE	targets	cell_type	0.70
ENDOTHELIAL	activates	cell_type	0.70

Targeting Hypotheses (12)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
LRRK2 G2019S Kinase Inhibition for Parkinson's Disease	0.795	neurodegeneration	Test
G2019S primarily raises baseline LRRK2 kinase activity rathe	0.790	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
Therapeutic Window Exists Because Amplified Signals (Not Bas	0.780	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
RAB29 Is the Critical Molecular Switch That Determines Wheth	0.710	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
LRRK2 kinase inhibition to normalize lysosomal trafficking i	0.710	neurodegeneration	Test

A downstream LRRK2-Rab10-JIP4 lysosomal stress loop promotes	0.680	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation	0.666	neurodegeneration	Does LRRK2's role as a lysosomal volume
LRRK2 Haploinsufficiency Traps Microglia in Senescence-Like	0.650	parkinsons	-
LRRK2 G2019S Uncouples RAB29-Dependent Spatial Control from	0.640	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
LRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysos	0.620	neurodegeneration	Test Hypothesis Fixtures
Dual-Mechanism Model: G2019S Increases Both Baseline AND Sig	0.550	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
MiT-TFE/LRRK2 Lysosomal Enhancement Therapy	0.000	-	Immune atlas neuroinflammation analysis

Mentioning Analyses (8)

Scientific analyses that reference this entity

LRRK2 Risk Variants: Lysosomal Membrane Dynamics in DA vs Striatal Neurons

neurodegeneration | 2026-04-27 | 0 hypotheses

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

neurodegeneration | 2026-04-24 | 5 hypotheses Top: 0.790

Does LRRK2's role as a lysosomal volume sensor explain the pathogenic mechanism

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.666

Neuroinflammation and microglial priming in early Alzheimer's Disease

neurodegeneration | 2026-04-04 | 20 hypotheses Top: 0.651

Immune atlas neuroinflammation analysis in neurodegeneration

Neuroinflammation | 2026-04-03 | 14 hypotheses Top: 0.681

Experiments (2)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Continual correlation noted between LRRK2 mutations and pain emergence	genetic_association	Parkinson's disease	0.500	0.00	human	extracted	N/A
LRRK2/GBA Mutation Carrier Resilience — Why Some Carriers Never Develo	validation	Parkinson's Disease	0.400	0.50	human	completed	$2,730,000

Related Papers (8)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopa [PMID:41128923]	Buck SA, Malankhanova T, Strader S, Ma E	Acta neuropathologica	2025
RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome hom [PMID:39343966]	Li X, Zhu H, Huang BT, Li X, Kim H, Tan	Nature communications	2024
Exploring the focal role of LRRK2 kinase in Parkinson's disease. [PMID:35147886]	["Kumar Sachin", "Behl Tapan", "Sehgal A	Environmental science and poll	2022
Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease. [PMID:35521944]	Wang S, Unnithan S, Bryant N	Mov Disord	2022
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020
Rab GTPases as Physiological Substrates of LRRK2 Kinase. [PMID:31138985]	Seol W, Nam D, Son I	Exp Neurobiol	2019
Multiple Sclerosis Pathology. [PMID:29358320]	Lassmann H	Cold Spring Harbor perspective	2018

Debates (9)

Multi-agent debates referencing this entity

How do GWAS-identified PD risk variants at the LRRK2 locus alter lysosomal membr

closed · Rounds: 6 · Score: 0.89 · 2026-04-27

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

closed · Rounds: 4 · Score: 0.74 · 2026-04-24

While the study establishes LRRK2 as a lysosomal swelling sensor and notes that

closed · Rounds: 4 · Score: 0.85 · 2026-04-16

Investigate mechanistic links between early microglial priming states, neuroinfl

closed · Rounds: 4 · Score: 0.86 · 2026-04-12

Investigate mechanistic links between early microglial priming states, neuroinfl

closed · Rounds: 5 · Score: 0.95 · 2026-04-12

Can speech, gait, retinal imaging, sleep, and smartphone data detect neurodegene

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

Comprehensive analysis of immune cell subtypes in neurodegeneration: microglia s

closed · Rounds: 4 · Score: 0.85 · 2026-04-03

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD trans

closed · Rounds: 4 · Score: 0.95 · 2026-04-03

Cell-type specific expression patterns of neurodegeneration genes in SEA-AD

closed · Rounds: 3 · Score: 0.68 · 2026-04-02

Related Research

Hypotheses and analyses mentioning LRRK2 in their description or question text

LRRK2

Understanding Entity Pages

Summary

Wiki Pages (21)

LRRK2 — Leucine Rich Repeat Kinase 2

LRRK2 Kinase Activation and Endolysosomal Dysfunction in Parkinson's Disease

LRRK2 Pathway in Parkinson's Disease

LRRK2 G2019S

LRRK2 Transgenic Mouse Model for Parkinson's Disease

LRRK2 Consortium

Parabacteroides goldsteinii Mitigation of Parkinsonism in LRRK2 Mice

LRRK2-GBA Combination Therapy for Parkinson's Disease

LRRK2 (Leucine-Rich Repeat Kinase 2) — Comprehensive Gene Review

LRRK2 Kinase-Targeting Therapies

LRRK2 Kinase Pathway in Parkinson's Disease

LRRK2→Kinase→Autophagy→PD Causal Chain

LRRK2 Signaling Pathway in Parkinson's Disease

LRRK2 Therapeutics: Investment Landscape Analysis

alpha-synuclein-LRRK2 Crosstalk

LRRK2 Pathway in PD

LRRK2 Signaling Pathway in Parkinson's Disease

AAV-LRRK2 IND-Enabling Study Design

LRRK2/GBA Mutation Carrier Resilience — Why Some Carriers Never Develop PD

LRRK2 Inhibitor Therapy

LRRK2 Kinase Inhibition in Parkinson's Disease - Therapeutic Mechanism

Pathway Diagram

Outgoing (1699)

Incoming (926)

Targeting Hypotheses (12)

Mentioning Analyses (8)

LRRK2 Risk Variants: Lysosomal Membrane Dynamics in DA vs Striatal Neurons

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

Does LRRK2's role as a lysosomal volume sensor explain the pathogenic mechanism

Neuroinflammation and microglial priming in early Alzheimer's Disease

Immune atlas neuroinflammation analysis in neurodegeneration

Cell type vulnerability in Alzheimer's Disease (SEA-AD data - v2)

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Digital biomarkers and AI-driven early detection of neurodegeneration

Experiments (2)

Related Papers (8)

Debates (9)

How do GWAS-identified PD risk variants at the LRRK2 locus alter lysosomal membr

Do pathogenic LRRK2 mutations amplify volume-sensing signals or just elevate bas

While the study establishes LRRK2 as a lysosomal swelling sensor and notes that

Investigate mechanistic links between early microglial priming states, neuroinfl

Investigate mechanistic links between early microglial priming states, neuroinfl

Can speech, gait, retinal imaging, sleep, and smartphone data detect neurodegene

Comprehensive analysis of immune cell subtypes in neurodegeneration: microglia s

What cell types are most vulnerable in Alzheimer's Disease based on SEA-AD trans

Cell-type specific expression patterns of neurodegeneration genes in SEA-AD

Related Research

A downstream LRRK2-Rab10-JIP4 lysosomal stress loop promotes alpha-synuclein rel

LRRK2 Volume Sensor Hijacking Drives Metabolic Dysregulation via SIRT1/PGC1α Sup

LRRK2 G2019S Uncouples RAB29-Dependent Spatial Control from Kinase Activity (H7)

LRRK2 Kinase Inhibition Reduces α-Synuclein Spread via Lysosomal Enhancement

Dual-Mechanism Model: G2019S Increases Both Baseline AND Signal-Dependent Phosph

MiT-TFE/LRRK2 Lysosomal Enhancement Therapy