| 2012 |
RILPL1 localizes specifically to the distal end of the mother centriole and to the primary cilium. Depletion of RILPL1 (and RILPL2) causes accumulation of signaling proteins in the ciliary membrane and prevents proper epithelial cell organization in 3D culture, indicating RILPL1 regulates ciliary membrane protein concentration by promoting protein removal from the primary cilium. |
Live-cell microscopy, siRNA depletion, immunofluorescence, 3D culture assays |
Molecular biology of the cell |
High |
23264467
|
| 2019 |
LRRK2-phosphorylated RAB8A and RAB10 are recruited to centrosome-localized RILPL1, causing centrosomal cohesion deficits in dividing cells and ciliogenesis defects. Both phenotypes depend on RAB8, RAB10, and RILPL1, and are reversed by LRRK2 kinase inhibition. |
Immunofluorescence, phospho-RAB antibodies, RNAi/KO, patient-derived peripheral cells, primary astrocytes from mutant LRRK2 mice, LRRK2 inhibitor treatment |
Human molecular genetics |
High |
31428781
|
| 2021 |
LRRK2-phosphorylated Rab10 recruits RILPL1 to the mother centriole, where the phospho-Rab10/RILPL1 complex blocks CP110 uncapping by preventing TTBK2 recruitment, thereby inhibiting early ciliogenesis. RILPL1 overexpression alone recapitulates the CP110 retention phenotype. |
Live-cell fluorescence microscopy, genetic knockouts (Rab10 KO, RILPL1 KO), LRRK2 kinase inhibition, MEF cells from R1441C LRRK2 knock-in mice |
Proceedings of the National Academy of Sciences of the United States of America |
High |
33653948
|
| 2022 |
RILPL1 localizes to the subdistal appendage of the mother centriole and mediates centrosomal accumulation of LRRK2-phosphorylated Rab10 (and Rab8), causing centrosome cohesion deficits and impairing cell polarization. The cohesion defects are specific to RILPL1 (not RILPL2) and require the GTP conformation and phosphorylation status of the Rab proteins. |
Immunofluorescence, scratch wound assays, transfection of dominant-active/inactive Rab mutants, LRRK2 kinase inhibition, siRNA knockdown |
Biology open |
High |
35776681
|
| 2022 |
Pathogenic LRRK2-mediated centrosomal cohesion deficits require RILPL1 and phospho-Rab proteins; mechanistically, the phospho-Rab/RILPL1 complex causes centrosomal displacement of CDK5RAP2, a protein critical for centrosome cohesion, without disrupting proteinaceous linker proteins. |
Co-immunoprecipitation, immunofluorescence, siRNA knockdown, iPS cell-derived models, transfected cell lines |
iScience |
High |
35721463
|
| 2023 |
LRRK2-phosphorylated Rab12 (at Ser106) binds RILPL1 with enhanced affinity, recruiting it to lysosomes and causing perinuclear lysosomal clustering. Knockout of RAB12 or RILPL1 abolishes the perinuclear clustering, demonstrating a Rab12-RILPL1 axis controlling lysosomal transport. |
RAB12 KO cells, RILPL1 KO, re-expression of phospho-mimetic/phospho-dead Rab12 mutants, immunofluorescence, Co-IP |
FASEB journal |
High |
37086089
|
| 2023 |
The Parkinson's VPS35[D620N] mutation drives LRRK2-mediated lysosomal recruitment of phospho-Rabs, which recruit RILPL1 to the lysosomal surface where it binds the lysosomal integral membrane protein TMEM55B via conserved regions. VPS35[D620N] reduces RILPL1 protein levels via proteasomal degradation (reversed by LRRK2 inhibition and proteasome inhibitors), and RILPL1 knockout enhances phospho-Rab substrate levels. |
Lysosomal proteomics, Co-IP, mutagenesis of RILPL1-TMEM55B interface, knockout mouse models (brain, lung, fibroblasts), LRRK2 inhibitor and proteasome inhibitor treatment |
Science advances |
High |
38091401
|
| 2025 |
Crystal structures of TMEM55B cytosolic domain (residues 80–166) alone and in complex with a C-terminal RILPL1 peptide (TMEM55B-binding motif, TBM) reveal that the RILPL1 TBM binds a shallow groove across two tandem RING-like Zn2+-stabilized β-sandwich domains of TMEM55B via backbone hydrogen bonding anchored by two glutamate residues. TMEM55B also independently forms complexes (via conserved TBM) with JIP3, JIP4, OCRL, WDR81, and TBC1D9B. |
X-ray crystallography, Co-immunoprecipitation, mass spectrometry, mutagenesis |
Structure (London, England : 1993) |
High |
41314214
|
| 2024 |
RILPL1 is recruited to LRRK2-positive damaged lysosomes via phospho-Rab proteins and promotes retraction of lysosomal tubulation/sorting (LYTL) tubules by binding to p150Glued (a dynactin subunit), facilitating dynein-dependent transport of lysosomes and tubules toward the minus-end of microtubules, opposing JIP4-driven kinesin-mediated tubule extension. |
Lysosomal proteomics (LRRK2 kinase inhibition), live-cell fluorescence microscopy, Co-IP (RILPL1–p150Glued), overexpression, KO cells, LLOMe lysosomal damage model |
The Journal of cell biology |
High |
40990465
|
| 2024 |
RAB12 cooperates with LRRK2 to inhibit primary ciliogenesis and regulate centrosome homeostasis in astrocytes by enhancing Rab10 phosphorylation and recruiting RILPL1; deletion of Rab12 in astrocytes prevents the ciliary and centrosomal deficits caused by LRRK2-G2019S. |
Cryo-EM structure of RAB12-LRRK2 complex, phosphoproteomics, astrocyte-specific Rab12 KO, immunofluorescence |
bioRxiv (preprint)preprint |
Medium |
bio_10.1101_2024.07.17.603999
|
| 2022 |
CGG repeat expansion in the 5′ UTR of RILPL1 causes oculopharyngodistal myopathy type 4 (OPDM4). The expanded repeat is translated into a toxic poly-glycine protein that co-localizes with p62 in intranuclear inclusions, and expanded repeat RNA also forms toxic RNA foci, suggesting dual protein and RNA gain-of-function mechanisms. |
Long-read whole-genome sequencing, RP-PCR, AL-PCR, methylation analysis, immunofluorescence, muscle biopsy |
American journal of human genetics |
Medium |
35148830 35700120
|