Affinage

LRRK1

Leucine-rich repeat serine/threonine-protein kinase 1 · UniProt Q38SD2

Length
2015 aa
Mass
225.4 kDa
Annotated
2026-06-10
36 papers in source corpus 21 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRRK1 is a multi-domain serine/threonine kinase that operates at the intersection of endosomal trafficking, cytoskeletal regulation, and bone homeostasis, and whose catalytic output is gated by both GTP binding and a network of upstream phosphorylation events (PMID:16243488, PMID:31085713, PMID:26192437). GTP binding to its Roc domain stimulates kinase activity, defining a GTP/GDP cycle that switches the enzyme between active and inactive states (PMID:16243488). Activity is further tuned by upstream kinases: PKC isoforms phosphorylate Ser1064/Ser1074/Thr1075 in the CORB GTPase domain to activate LRRK1 (PMID:36040231), PLK1 phosphorylates Ser1790 to enable CDK1-dependent activation at centrosomes and at the cilia base (PMID:26192437, PMID:36254578), and EGFR phosphorylates Tyr944 to suppress activity, forming a feedback loop during endosomal trafficking that is relieved by PTP1B-mediated dephosphorylation at ER-endosome contact sites (PMID:22337768, PMID:36744428). Structurally, LRRK1 is autoinhibited in a dimer-dependent manner distinct from the monomeric autoinhibition of LRRK2 (PMID:37857821). A principal substrate is Rab7A, phosphorylated at Ser72, which couples LRRK1 to dynein-dynactin-driven perinuclear transport of EGFR-containing endosomes and to ULK1/ULK2-dependent Parkin-mediated mitophagy (PMID:31085713, PMID:36408770). Through additional substrates LRRK1 controls microtubule-based processes—CDK5RAP2 (Ser140) for centrosomal microtubule nucleation and spindle orientation (PMID:26192437), CLIP-170 (Thr1384) for dynactin recruitment to migrating endosomes (PMID:25413345), and NDEL1 (Ser155) for dynein-2-dependent cilia disassembly (PMID:36254578). In osteoclasts LRRK1 phosphorylates L-plastin at Ser5 to regulate the actin cytoskeleton, and biallelic loss-of-function LRRK1 mutations cause osteosclerotic metaphyseal dysplasia through defective osteoclast bone resorption (PMID:30136304, PMID:27055475, PMID:32119750). LRRK1 also functions as a scaffold rather than purely as a kinase, recruiting EGFR to ESCRT-0 machinery for multivesicular body sorting and synergizing with CARMA1 to drive BCR-induced NF-κB activation in B cells (PMID:21245839, PMID:27166870).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 High

    Established LRRK1 as a bona fide kinase whose activity is controlled by an intramolecular GTPase switch, framing it as a GTP-regulated enzyme rather than a passive scaffold.

    Evidence In vitro kinase and GDP/GTP binding assays with Roc-domain mutagenesis and Parkinson's-equivalent mutations

    PMID:16243488

    Open questions at the time
    • Did not identify physiological substrates
    • GTP/GDP cycle dynamics in cells not measured
    • No structural basis for Roc-to-kinase coupling
  2. 2011 High

    Defined LRRK1's first cellular role: a kinase-dependent regulator and scaffold for EGFR transit through the endosomal system toward multivesicular bodies.

    Evidence Co-IP via Grb2, co-internalization imaging, RNAi with EGFR trafficking readout, and kinase-dead rescue

    PMID:21245839

    Open questions at the time
    • Endosomal substrate of LRRK1 not yet identified
    • Mechanism of ESCRT-0 facilitation unresolved
  3. 2012 High

    Revealed a feedback loop in which EGFR phosphorylates LRRK1 at Tyr944 to dampen its activity, coupling receptor signaling to control of endosome motility.

    Evidence Y944F mutagenesis, in vitro kinase assay, phospho-detection, and endosome motility imaging

    PMID:22337768

    Open questions at the time
    • Phosphatase reversing pY944 not identified at this stage
    • Structural effect of pY944 on kinase domain unknown
  4. 2014 High

    Distinguished LRRK1 from its paralog LRRK2 by partner specificity (EGFR vs 14-3-3) and identified CLIP-170 as a substrate linking LRRK1 to dynein/dynactin-driven endosome migration.

    Evidence Protein microarray and Co-IP/MS interaction screens, EGF-induced translocation imaging, and in vitro CLIP-170 phosphorylation with functional readout

    PMID:24947832 PMID:25413345

    Open questions at the time
    • How pTyr944 and CLIP-170 phosphorylation are temporally coordinated unclear
    • Direct dynactin-CLIP-170 stoichiometry not resolved
  5. 2014 Medium

    Showed LRRK1 activity can be modulated by FIH-1 disruption of the EGFR/LRRK1 complex, linking it to EGFR turnover and keratinocyte migration.

    Evidence Co-IP, scratch-wound migration assay, ERK readouts, and FIH-1 null wound-healing phenotype

    PMID:25455687

    Open questions at the time
    • Molecular detail of how FIH-1 displaces the complex limited
    • Whether LRRK1 kinase activity changes upon FIH-1 binding not tested
  6. 2015 High

    Placed LRRK1 in a mitotic kinase cascade: PLK1/CDK1 activate it at centrosomes, and it phosphorylates CDK5RAP2 to control microtubule nucleation and spindle orientation.

    Evidence Reconstituted in vitro kinase cascade, phospho-antibodies, centrosome fractionation, and spindle-orientation phenotypes with mutant rescue

    PMID:26192437

    Open questions at the time
    • Roc/GTP contribution to centrosomal activation not dissected
    • Whether the same activation applies outside mitosis unknown
  7. 2016 High

    Connected LRRK1 to human disease and to immune signaling: loss-of-function causes osteosclerotic metaphyseal dysplasia via defective osteoclast resorption, and LRRK1 synergizes with CARMA1 to drive BCR-induced NF-κB.

    Evidence Whole-exome sequencing plus Lrrk1-KO osteoclast assays; Lrrk1-KO mouse B-cell phenotyping with LRRK1-CARMA1 Co-IP

    PMID:27055475 PMID:27166870

    Open questions at the time
    • Osteoclast substrate not identified in 2016
    • Mechanism of CARMA1 synergy and whether it is kinase-dependent unresolved
  8. 2017 Medium

    Provided the first architectural view, showing LRRK1 forms a two-fold symmetric homodimer broadly resembling the LRRK2 dimer.

    Evidence Low-resolution (25 Å) cryo-EM single-particle analysis of full-length LRRK1

    PMID:28819229

    Open questions at the time
    • Resolution too low for domain-level mechanism
    • Autoinhibition not addressed
    • Functional consequences of dimerization not tested
  9. 2018 Medium

    Expanded LRRK1's substrate and interaction repertoire to osteoclast actin (L-plastin Ser5) and to lysosomal exocytosis control via VAMP7 binding.

    Evidence Phosphoproteomics of WT vs Lrrk1-KO osteoclasts with KO mouse micro-CT; LRRK1-VAMP7 Co-IP with secretion and rigidity assays

    PMID:30136304 PMID:30240735

    Open questions at the time
    • VAMP7 regulation shown by a single lab without reciprocal validation
    • Direct kinase dependence of VAMP7 effect not established
  10. 2019 High

    Identified Rab7A Ser72 as a central LRRK1 substrate that recruits RILP and dynein-dynactin to drive perinuclear endosome transport, mechanistically unifying earlier trafficking observations.

    Evidence In vitro kinase assay, phospho-Rab7 S72 antibody, RILP Co-IP, and endosome motility imaging with dominant-negative/RNAi

    PMID:31085713

    Open questions at the time
    • Reconciling RILP-promoting vs RILP-neutral effects of pRab7A across studies
    • In vivo relevance of Rab7 phosphorylation not yet defined
  11. 2020 High

    Demonstrated in patient-derived cells that LRRK1 kinase activity is required for L-plastin Ser5 phosphorylation and normal osteoclast resorption, directly tying the kinase to human bone disease.

    Evidence Patient osteoclasts with a kinase-disrupting splice mutation, phospho-L-plastin western blot, and bone resorption pit assays

    PMID:32119750

    Open questions at the time
    • Whether other substrates contribute to the osteoclast defect not resolved
    • Mechanism linking L-plastin pSer5 to resorption pit formation incomplete
  12. 2021 High

    Defined LRRK1 substrate specificity and upstream regulation, showing it phosphorylates Rab7A (not Rab8A/Rab10), is activated by phorbol esters, is dephosphorylated by PPM1H, and is regulated independently of LRRK2's Rab29/VPS35 inputs.

    Evidence MS of LRRK1-KO vs WT cells, in vitro kinase profiling across Rab substrates, phorbol-ester stimulation, and inhibitor profiling

    PMID:33459343

    Open questions at the time
    • Discrepancy with prior report on pRab7A-RILP coupling
    • Identity of the PKC-coupled upstream signal not pinned down here
  13. 2022 High

    Integrated LRRK1 into multiple Rab7-dependent and cytoskeletal pathways: ULK1/2-ATG13-recruited mitophagy, PLK1-driven NDEL1 Ser155 phosphorylation for cilia disassembly, and PKC-mediated CORB-domain activation.

    Evidence Genetic epistasis and ectopic mitochondrial targeting for mitophagy; in vitro NDEL1 phosphorylation with dynein-2 Co-IP and cilia resorption; PKC isoform reconstitution with activation-site mutagenesis

    PMID:36040231 PMID:36254578 PMID:36408770

    Open questions at the time
    • How distinct activation cues (PKC, PLK1, ULK) select specific substrate outputs unclear
    • Spatial control restricting each substrate engagement not fully mapped
  14. 2023 High

    Resolved LRRK1's unique regulatory logic—dimer-dependent autoinhibition distinct from LRRK2—and placed EGFR/LRRK1 reactivation at ER-endosome contact sites via PTP1B.

    Evidence Cryo-EM of monomeric and dimeric LRRK1 with LRRK2 comparison; Co-IP, proximity ligation, and trafficking assays for the PTP1B-EGFR-LRRK1 axis

    PMID:36744428 PMID:37857821

    Open questions at the time
    • How phosphorylation events relieve dimer autoinhibition structurally not shown
    • Dynamics of LRRK1 monomer-dimer transition in cells unmeasured
  15. 2025 Low

    Began broadening the substrate landscape by proposing Rab43 as a new LRRK1 target distinct from LRRK2's Rab set.

    Evidence In vitro kinase profiling against a Rab panel with MS phosphorylation profiling (preprint)

    Open questions at the time
    • No cellular validation of Rab43 phosphorylation by LRRK1
    • Preprint, not yet peer-reviewed
    • Physiological role of any Rab43 phosphorylation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LRRK1's multiple upstream activation inputs (GTP, PKC, PLK1) are spatially and temporally coordinated to select among its diverse substrates across trafficking, mitosis, ciliogenesis, mitophagy, and bone remains unresolved.
  • No unified model linking activation cue to substrate choice
  • Limited in vivo substrate-phosphorylation data outside osteoclasts
  • Structural mechanism coupling Roc/CORB phosphorylation to kinase activation not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016740 transferase activity 3 GO:0060090 molecular adaptor activity 2 GO:0003924 GTPase activity 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005768 endosome 4 GO:0005739 mitochondrion 1 GO:0005783 endoplasmic reticulum 1 GO:0005815 microtubule organizing center 1 GO:0005929 cilium 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 1 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Partners
ATG13CARMA1CDK5RAP2CLIP-170EGFRNDEL1RAB7AVAMP7

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 LRRK1 is both a functional protein kinase and a GDP/GTP-binding protein; GTP binding to the Roc domain specifically stimulates LRRK1 kinase activity, proposing a model in which LRRK1 cycles between GTP-bound active and GDP-bound inactive states. In vitro kinase assay, GDP/GTP binding assay, Roc domain mutagenesis, and introduction of LRRK2 Parkinson's-equivalent mutations that downregulate LRRK1 kinase activity Cellular signalling High 16243488
2011 LRRK1 forms a complex with activated EGFR via Grb2, is co-internalized with EGF into early endosomes, regulates EGFR transport from early to late endosomes in a kinase-dependent manner, and serves as a scaffold facilitating EGFR interaction with the ESCRT-0 complex for sorting into multivesicular body intraluminal vesicles. Co-immunoprecipitation, fluorescence microscopy/co-localization, RNAi knockdown with EGFR trafficking readout, kinase-dead mutant rescue experiments Nature communications High 21245839
2012 EGFR phosphorylates LRRK1 at Tyr-944, reducing LRRK1 kinase activity; mutation Y944F abolishes this phosphorylation, causing hyperactivation of LRRK1, enhanced endosome motility toward the perinuclear region, and defective multivesicular body formation — establishing a feedback loop where EGFR downregulates LRRK1 during endosomal trafficking. Site-directed mutagenesis (Y944F), in vitro kinase assay, phospho-specific detection, fluorescence microscopy of endosome motility, dominant-negative and rescue experiments Molecular biology of the cell High 22337768
2014 LRRK1 phosphorylates CLIP-170 at Thr1384 in its C-terminal zinc knuckle motif, promoting CLIP-170 association with dynein-dynactin complexes and accumulation of p150Glued at microtubule plus ends, thereby facilitating migration of EGFR-containing endosomes. In vitro kinase assay identifying CLIP-170 as LRRK1 substrate, phospho-specific antibody, Co-IP, fluorescence microscopy of endosome movement, RNAi knockdown Journal of cell science High 25413345
2014 EGFR is a LRRK1-specific interactor (not LRRK2), while 14-3-3 proteins are LRRK2-specific; EGF stimulation induces translocation of LRRK1 (but not LRRK2) to endosomes, confirming distinct cellular functions; phosphosite mapping of LRRK1 reveals phosphosites outside 14-3-3 consensus binding motifs. Protein microarray-based interaction screen, co-immunoprecipitation followed by mass spectrometry, stable cell lines expressing 3xFlag-LRRK1 or LRRK2, EGF-induced translocation imaging Journal of neurochemistry High 24947832
2015 LRRK1 is a PLK1 substrate phosphorylated at Ser1790; PLK1 phosphorylation enables CDK1-mediated activation of LRRK1 at centrosomes; activated LRRK1 phosphorylates CDK5RAP2 at Ser140 in its γ-tubulin-binding motif, promoting CDK5RAP2–γ-tubulin interaction and astral microtubule nucleation to regulate mitotic spindle orientation. In vitro kinase assay (PLK1→LRRK1, LRRK1→CDK5RAP2), phospho-specific antibodies, centrosome fractionation, spindle orientation microscopy, RNAi knockdown and rescue with phosphomimetic/phospho-dead mutants Nature cell biology High 26192437
2017 Full-length LRRK1 forms a homodimer with two-fold symmetry, structurally similar to the LRRK2 dimer; cryo-EM at 25 Å resolution reveals overall dimeric architecture, suggesting dimerization mechanisms are conserved between LRRK1 and LRRK2. Cryo-electron microscopy and single particle analysis of purified full-length LRRK1 protein Scientific reports Medium 28819229
2018 LRRK1 binds the Longin domain of VAMP7 and negatively regulates VAMP7-mediated lysosomal exocytosis; LRRK1 and VARP compete for VAMP7 binding in a tug-of-war mechanism that controls the peripheral pool of secretory lysosomes and cellular response to substrate rigidity. Co-immunoprecipitation (LRRK1-VAMP7 interaction), VAMP7 knockdown/rescue with Longin domain mutants, atomic force microscopy for substrate rigidity, secretion assays iScience Medium 30240735
2018 LRRK1 phosphorylates L-plastin at Ser5 in osteoclasts; Lrrk1-deficient osteoclasts lack L-plastin Ser5 phosphorylation; L-plastin knockout mice show increased trabecular bone volume, linking LRRK1-mediated L-plastin phosphorylation to actin assembly and osteoclast function. Metal affinity purification coupled LC/MS of phosphoproteins from wild-type vs Lrrk1-KO osteoclasts, phospho-specific western blotting, micro-CT of L-plastin KO mice Journal of cellular biochemistry Medium 30136304
2019 LRRK1 phosphorylates GTP-bound Rab7 at Ser72 at the endosomal membrane; this phosphorylation promotes Rab7 interaction with its effector RILP, leading to dynein-dynactin recruitment to Rab7-positive vesicles and dynein-driven transport of EGFR-containing endosomes toward the perinuclear region. In vitro kinase assay (LRRK1 + Rab7), phospho-Rab7 S72 antibody, Co-IP of RILP with phospho-Rab7, fluorescence microscopy of endosome motility, dominant-negative and RNAi experiments Journal of cell science High 31085713
2010 LRRK1 and LRRK2 physically interact and form heterodimers, as demonstrated by co-immunoprecipitation. Co-immunoprecipitation of LRRK1-LRRK2 heterodimer in transfected cells Mechanisms of ageing and development Low 20144646
2016 Biallelic loss-of-function mutations in LRRK1 cause osteosclerotic metaphyseal dysplasia in humans; in vitro functional studies using osteoclasts from Lrrk1-deficient mice confirmed that the human deletion is a loss-of-function mutation, establishing LRRK1 as essential for osteoclast-mediated bone resorption and bone mass regulation. Whole-exome sequencing to identify mutation, in vitro osteoclast functional assay from Lrrk1-KO mice, comparison with Lrrk1-deficient mouse skeletal phenotype Journal of medical genetics High 27055475
2016 LRRK1 is required for BCR-mediated NF-κB activation; Lrrk1-deficient mice have impaired B-cell proliferation, survival, IgG3 class-switch recombination, and NF-κB target gene expression; LRRK1 physically interacts with CARMA1 and potently synergizes with it to enhance NF-κB activation. Lrrk1 knockout mouse model, BCR stimulation assays, NF-κB reporter and target gene expression, Co-immunoprecipitation of LRRK1-CARMA1, B-cell differentiation and immunoglobulin production assays Scientific reports High 27166870
2020 A LRRK1 splice-site mutation causing loss of kinase function results in strongly reduced phosphorylation of L-plastin at Ser5 in patient-derived osteoclasts, which show markedly abnormal morphology and impaired bone resorption (superficial erosion only, no resorption pits), directly linking LRRK1 kinase activity to osteoclast actin cytoskeleton function in humans. Patient-derived osteoclast differentiation from peripheral blood monocytes, phospho-L-plastin Ser5 western blot, bone resorption pit assay, cDNA sequencing of splice mutation Journal of bone and mineral research High 32119750
2021 LRRK1 specifically phosphorylates Rab7A at Ser72 (but not Rab8A or Rab10); phorbol ester stimulation of mouse embryonic fibroblasts markedly enhances Rab7A Ser72 phosphorylation via LRRK1; LRRK1 mutations equivalent to LRRK2 Parkinson's mutations (K746G and I1412T) enhance LRRK1-mediated Rab7A phosphorylation; Rab29 and VPS35[D620N] do not regulate LRRK1 (unlike LRRK2); PPM1H phosphatase dephosphorylates phospho-Rab7A; LRRK1 phosphorylation of Rab7A does not affect its interaction with effector RILP. Mass spectrometry of LRRK1-KO vs wild-type cells, recombinant LRRK1 in vitro kinase assay with multiple Rab substrates, phospho-specific antibody, phorbol ester stimulation, LRRK2 inhibitor panel, GZD-824 inhibitor characterization The Biochemical journal High 33459343
2022 Multiple PKC isoforms phosphorylate and activate LRRK1 by phosphorylating Ser1064, Ser1074, and Thr1075 in the CORB GTPase domain (not the kinase domain); Thr1075 mutation to Ala blocks PKC-mediated activation; phosphomimetic triple Glu mutation enhances LRRK1 kinase activity ~3-fold; PKC inhibitors including darovasertib block LRRK1 activation in HEK293 cells. In vitro kinase assay (multiple PKC isoforms + recombinant LRRK1), phosphatase reversal, site-directed mutagenesis (Ala and Glu substitutions), cell-based kinase activity assay with PKC inhibitors The Biochemical journal High 36040231
2022 LRRK1 functions downstream of ULK1/ULK2 in Parkin-mediated mitophagy; the ULK complex recruits LRRK1 to mitochondria via ATG13 interaction; LRRK1 phosphorylates Rab7 Ser72 at mitochondria to initiate mitophagosome formation; ectopic targeting of active LRRK1 to mitochondria is sufficient to induce Rab7 Ser72 phosphorylation and bypass ATG13 requirement. Genetic epistasis (ULK1/ULK2 KO, ATG13 KO), mitophagy assays, ectopic LRRK1 mitochondrial targeting construct, phospho-Rab7 S72 detection, Co-IP of LRRK1 with ATG13 Journal of cell science High 36408770
2022 LRRK1 phosphorylates NDEL1 at Ser155; this phosphorylation promotes NDEL1 interaction with intermediate chains of cytoplasmic dynein-2 and drives cilia disassembly via retrograde intraflagellar transport; PLK1 phosphorylates and activates LRRK1 at the cilia base during serum-induced ciliary resorption, defining a PLK1-LRRK1-NDEL1 pathway in cilia disassembly. RNAi depletion of LRRK1 with cilia resorption assay, in vitro kinase assay (LRRK1→NDEL1 Ser155), phospho-specific detection, Co-IP of NDEL1 with dynein-2 intermediate chains, PLK1 inhibitor experiments Journal of cell science High 36254578
2023 Cryo-EM structures of monomeric and dimeric LRRK1 show that, unlike LRRK2 (which is sterically autoinhibited as a monomer), LRRK1 is autoinhibited in a dimer-dependent manner and has an additional level of autoinhibition absent in LRRK2 that prevents kinase activation. Cryo-EM structure determination of monomeric and dimeric full-length LRRK1, structural comparison with LRRK2 cryo-EM structures, evolutionary analysis Nature structural & molecular biology High 37857821
2023 LRRK1 acts as a scaffold at ER-endosome contact sites to facilitate PTP1B-mediated dephosphorylation of EGFR (at pY944 on LRRK1 and on EGFR itself); LRRK1 is required for the PTP1B-EGFR interaction in response to EGF; PTP1B in turn reactivates LRRK1 by dephosphorylating pY944, promoting EGFR-endosome transport to the perinuclear region; this establishes the ER-endosome contact site as a hub for LRRK1-dependent EGFR trafficking regulation. Co-immunoprecipitation (PTP1B-EGFR-LRRK1), proximity ligation assay at ER-endosome contact sites, phospho-specific antibodies, LRRK1 knockdown with rescue experiments, live-cell imaging of endosome motility Journal of cell science High 36744428
2014 FIH-1 (HIF1AN) binds LRRK1 and disrupts the EGFR/LRRK1 complex; this prevents proper EGFR turnover and enhances EGFR signaling through the MAPK pathway to promote keratinocyte migration. Co-immunoprecipitation (FIH-1/LRRK1 interaction), in vitro scratch wound assay, EGFR signaling readouts (ERK1/2 phosphorylation), FIH-1 null mouse wound healing phenotype The American journal of pathology Medium 25455687
2025 LRRK1 phosphorylates Rab43 (a novel LRRK1:Rab43 kinase pair identified in vitro); comprehensive substrate profiling shows LRRK1 and LRRK2 phosphorylate distinct sets of Rab GTPases. In vitro kinase profiling of recombinant LRRK1 against a panel of Rab GTPases, mass spectrometry-based phosphorylation profiling bioRxivpreprint Low

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Dynamic and redundant regulation of LRRK2 and LRRK1 expression. BMC neuroscience 121 18045479
2005 LRRK1 protein kinase activity is stimulated upon binding of GTP to its Roc domain. Cellular signalling 95 16243488
2007 Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1. Journal of neurochemistry 72 17394548
2011 Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor. Nature communications 69 21245839
2013 Expression analysis of Lrrk1, Lrrk2 and Lrrk2 splice variants in mice. PloS one 66 23675505
2015 PLK1-dependent activation of LRRK1 regulates spindle orientation by phosphorylating CDK5RAP2. Nature cell biology 59 26192437
2014 Differential protein-protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways. Journal of neurochemistry 44 24947832
2021 Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms. The Biochemical journal 42 33459343
2019 LRRK1 phosphorylation of Rab7 at S72 links trafficking of EGFR-containing endosomes to its effector RILP. Journal of cell science 42 31085713
2016 Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity. Journal of medical genetics 38 27055475
2017 Cryo-EM analysis of homodimeric full-length LRRK2 and LRRK1 protein complexes. Scientific reports 37 28819229
2018 Biomechanical Control of Lysosomal Secretion Via the VAMP7 Hub: A Tug-of-War between VARP and LRRK1. iScience 28 30240735
2016 Identification of a novel LRRK1 mutation in a family with osteosclerotic metaphyseal dysplasia. Journal of human genetics 27 27829680
2012 EGFR-dependent phosphorylation of leucine-rich repeat kinase LRRK1 is important for proper endosomal trafficking of EGFR. Molecular biology of the cell 24 22337768
2014 LRRK1-phosphorylated CLIP-170 regulates EGFR trafficking by recruiting p150Glued to microtubule plus ends. Journal of cell science 23 25413345
2007 Variants in the LRRK1 gene and susceptibility to Parkinson's disease in Norway. Neuroscience letters 23 17324517
2013 Rare variants in LRRK1 and Parkinson's disease. Neurogenetics 22 24241507
2016 LRRK1 is critical in the regulation of B-cell responses and CARMA1-dependent NF-κB activation. Scientific reports 20 27166870
2010 Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson disease. Mechanisms of ageing and development 20 20144646
2020 Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 16 32119750
2020 LINC00511 exacerbated T-cell acute lymphoblastic leukemia via miR-195-5p/LRRK1 axis. Bioscience reports 14 32242897
2019 A novel homozygous LRRK1 stop gain mutation in a patient suspected with osteosclerotic metaphyseal dysplasia. Annals of human genetics 14 31571209
2023 LRRK1 functions as a scaffold for PTP1B-mediated EGFR sorting into ILVs at the ER-endosome contact site. Journal of cell science 12 36744428
2018 LRRK1 regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L-plastin. Journal of cellular biochemistry 12 30136304
2022 The ULK complex-LRRK1 axis regulates Parkin-mediated mitophagy via Rab7 Ser-72 phosphorylation. Journal of cell science 11 36408770
2014 FIH-1 disrupts an LRRK1/EGFR complex to positively regulate keratinocyte migration. The American journal of pathology 11 25455687
2022 PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain. The Biochemical journal 10 36040231
2023 Structure of LRRK1 and mechanisms of autoinhibition and activation. Nature structural & molecular biology 9 37857821
2021 Broadening the phenotype of LRRK1 mutations - Features of malignant osteopetrosis and optic nerve atrophy with intrafamilial variable expressivity. European journal of medical genetics 9 34798323
2018 Genetic Analysis of LRRK1 and LRRK2 Variants in Essential Tremor Patients. Genetic testing and molecular biomarkers 8 29812962
2022 LRRK1-mediated NDEL1 phosphorylation promotes cilia disassembly via dynein-2-driven retrograde intraflagellar transport. Journal of cell science 5 36254578
2019 A small molecular inhibitor of LRRK1 identified by homology modeling and virtual screening suppresses osteoclast function, but not osteoclast differentiation, in vitro. Aging 5 31113907
2023 Protein kinase C showcases allosteric control: activation of LRRK1. The Biochemical journal 1 36762701
2023 Osteosclerotic Metaphyseal Dysplasia Due to a Likely Pathogenic LRRK1 Variant as a Cause of Recurrent Long Bone Fractures. JBMR plus 1 37614307
2023 Case Report: Osteosclerotic metaphyseal dysplasia with optic nerve involvement and progressive osteonecrosis of the jaw due to a novel LRRK1 mutation. Frontiers in endocrinology 1 37920250
2021 Chemical IN04 Inhibits the Kinase Domain not the ROC Domain of LRRK1: Results from Homology Modeling and Molecular Docking. Medicinal chemistry (Shariqah (United Arab Emirates)) 0 32972350

Missed literature

Know a paper Affinage missed for LRRK1? Flag it for the maintainers and the community.

No submissions yet.