Affinage

SORL1

Sortilin-related receptor · UniProt Q92673

Length
2214 aa
Mass
248.4 kDa
Annotated
2026-04-28
100 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SORL1 encodes SorLA, a multidomain type I transmembrane sorting receptor that functions as a master regulator of intracellular vesicular trafficking, directing the endosomal fate of APP and multiple other transmembrane cargoes including TRKB, GLUA1, HER2/HER3, insulin receptor, IL-6R, and the GDNF/GFRα1 complex (PMID:17220890, PMID:35226190, PMID:31138794, PMID:33420373, PMID:27322061, PMID:28265003, PMID:23333276). SorLA cycles between the TGN, endosomes, and the plasma membrane through interactions with the retromer complex (via a FANSHY–VPS26 interaction), GGA1/2, AP-1, and SNX27; retromer-dependent retrograde sorting retrieves APP from endosomes to the TGN to prevent amyloidogenic processing, while GGA-dependent anterograde sorting targets newly generated Aβ peptides to lysosomes for degradation via the VPS10p domain (PMID:22279231, PMID:11821067, PMID:17646382, PMID:27466343, PMID:26377460, PMID:24523320). SorLA dimerizes through its fibronectin-type-III and VPS10p domains within retromer-positive endosomal tubules to enhance APP recycling, and its ectodomain undergoes ADAM17-mediated shedding—modulated by ROCK2 phosphorylation at S2206 and tetraspanin CD9—releasing a soluble form (sSORLA) that activates EGFR/ERK signaling to promote neurite outgrowth (PMID:36652482, PMID:21147781, PMID:24699135, PMID:32601248). Loss-of-function variants and haploinsufficiency cause endosomal enlargement, increased Aβ production, elevated tau, and reduced APOE/CLU levels, establishing SORL1 as a causal Alzheimer's disease gene (PMID:34922638, PMID:36099918, PMID:37611586, PMID:32492427).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1999 Medium

    Before functional characterization, SorLA's expression pattern needed mapping; immunohistochemistry revealed that LR11/SorLA is a predominantly neuronal protein enriched in hippocampus and brainstem, establishing the brain as a primary site of function.

    Evidence Immunohistochemistry in rat and human brain with polyclonal anti-LR11 antibody

    PMID:10375696

    Open questions at the time
    • Single antibody used without knockout validation
    • Subcellular compartment identity of the cytoplasmic punctum unresolved
  2. 2000 Medium

    Early work established that SorLA undergoes metalloprotease-mediated ectodomain shedding and that this shedding is linked to mitogenic signaling via head activator, revealing SorLA as both a trafficking receptor and a signaling intermediate.

    Evidence Antisense knockdown, metalloprotease inhibition, and cell proliferation assays in neuronal cell lines

    PMID:11082041

    Open questions at the time
    • Shedding protease identity not defined
    • Head activator pathway relevance to mammalian physiology uncertain
  3. 2001 High

    Biochemical characterization showed that SorLA is furin-cleaved in the late Golgi to activate its VPS10p domain for ligand binding (including ApoE and RAP), and that the receptor can mediate endocytosis of ApoE-rich lipoproteins, establishing SorLA as a multifunctional endocytic receptor.

    Evidence Furin cleavage assays, ligand binding studies, lipoprotein internalization and cholesteryl ester accumulation assays in transfected cells

    PMID:11294867 PMID:11557679

    Open questions at the time
    • Physiological relevance of lipoprotein uptake in neurons versus peripheral tissues unclear
    • Post-furin trafficking itinerary not resolved
  4. 2002 High

    Identification of GGA1/2 binding to a ψ-ψ-X-X-φ motif in the SorLA cytoplasmic tail and the discovery that SorLA promotes uPAR-dependent cell migration established two key functional axes: Golgi-to-endosome sorting via coat adaptors and regulation of cell motility.

    Evidence Co-IP and pulldown with mutagenesis of tail residues; SMC migration/invasion assays with uPAR-blocking antibodies

    PMID:11821067 PMID:11956127

    Open questions at the time
    • Whether GGA and uPAR pathways are mechanistically linked was unknown
    • In vivo relevance of SorLA in vascular remodeling not yet tested
  5. 2006 High

    Biophysical studies defined the molecular basis of the SorLA–APP interaction: the complement-type repeat (CR) cluster forms a 1:1 complex with the APP carbohydrate-linked domain, sequestering APP in the Golgi and protecting it from amyloidogenic processing; simultaneously, SorLA was shown to be a γ-secretase substrate.

    Evidence SPR, analytical ultracentrifugation, FRET proximity assays; PS1/PS2 knockout cells and γ-secretase inhibitors

    PMID:16489755 PMID:16930450

    Open questions at the time
    • Whether γ-secretase cleavage of SorLA has a signaling function was unknown
    • CR-cluster domain requirement not yet tested by deletion mutagenesis
  6. 2007 High

    Functional studies demonstrated that SorLA directs APP into recycling pathways and that loss of SorLA shunts APP into Aβ-generating compartments; parallel work mapped the AP-1, GGA, and retromer (VPS35/SNX1) machinery controlling SorLA trafficking between Golgi and endosomes.

    Evidence Cell-based APP trafficking/Aβ assays with SORL1 knockdown/overexpression; chimeric receptor trafficking in AP-1-deficient cells, co-IP with retromer subunits

    PMID:17220890 PMID:17646382

    Open questions at the time
    • Precise retromer binding motif on SorLA unidentified
    • In vivo genetic evidence for SorLA's protective role lacking
  7. 2008 High

    In vivo genetic models validated SorLA as a dose-dependent regulator of APP processing and Aβ accumulation, and showed that soluble SorLA promotes vascular SMC migration via FAK/ERK/Rac1 and uPAR–integrin complexes.

    Evidence LR11-deficient mice crossed with APPswe/PS1ΔE9 AD model; LR11 knockout femoral artery cuff model with signaling assays

    PMID:18618022 PMID:19036982

    Open questions at the time
    • Mechanism by which SorLA dosage controls secretase access not defined
    • Whether vascular and neuronal functions intersect in AD pathogenesis unclear
  8. 2010 High

    ROCK2 was identified as a kinase that phosphorylates SorLA at S2206, regulating ectodomain shedding; this provided the first post-translational switch controlling SorLA surface levels and thereby Aβ reduction.

    Evidence LC-MS/MS kinase screen, co-IP from human brain, S2206A mutagenesis, in vitro kinase assay

    PMID:21147781

    Open questions at the time
    • Whether other kinases or phosphatases regulate SorLA tail phosphorylation unknown
    • Physiological signals activating ROCK2-SorLA axis in neurons not identified
  9. 2012 High

    The FANSHY motif in SorLA's cytoplasmic tail was mapped as the VPS26-binding site required for retromer-mediated endosome-to-TGN retrieval; disruption of this motif redistributed SorLA to endosomes and increased amyloidogenic processing, completing the molecular logic of SorLA's retrograde sorting.

    Evidence Motif identification, VPS26 knockdown, mutagenesis, APP processing assays

    PMID:22279231

    Open questions at the time
    • Structure of the VPS26–FANSHY complex unresolved
    • Whether other retromer subunits contribute to SorLA recognition unknown
  10. 2012 High

    GGA1 was shown to specifically mediate endocytic LR11 traffic affecting BACE1 localization and Aβ production, and SorLA was found to prevent APP oligomerization needed for efficient allosteric secretase cleavage, revealing a second mechanism (beyond compartmental segregation) by which SorLA suppresses Aβ generation.

    Evidence GGA-binding motif mutagenesis with siRNA; quantitative biochemical/mathematical modeling of APP oligomerization in cells and mouse brain

    PMID:21989385 PMID:22621900

    Open questions at the time
    • Structural basis of SorLA-mediated monomerization of APP unknown
    • Relative contributions of trafficking vs. oligomerization mechanisms not quantified in vivo
  11. 2013 High

    SorLA's cargo repertoire was expanded beyond APP to include the GDNF/GFRα1 complex (directing GDNF to lysosomes while recycling GFRα1) and soluble LR11-mediated uPAR-dependent HSPC adhesion, demonstrating SorLA as a general-purpose sorting receptor for diverse ligands.

    Evidence SorLA knockout mice with GDNF/RET trafficking and behavioral phenotyping; lr11−/− HSPC adhesion assays with HIF-1α ChIP

    PMID:23333276 PMID:23486467

    Open questions at the time
    • How SorLA discriminates among diverse cargoes for lysosomal versus recycling routes unclear
    • Neuronal consequences of GDNF mis-sorting in AD context not explored
  12. 2014 High

    SorLA's VPS10p domain was shown to directly bind Aβ peptides and direct them to lysosomes for degradation, and a familial AD mutation in this domain impaired Aβ binding, linking loss of Aβ-sorting function to disease; separately, α2A-adrenergic receptor activation was shown to disrupt the SorLA–APP complex and promote amyloidogenic processing.

    Evidence SORLA transgenic mice, domain binding assays, disease mutation testing; α2AAR knockout and pharmacological manipulation with APP-SorLA co-IP

    PMID:24523320 PMID:25404298

    Open questions at the time
    • Whether adrenergic modulation of SorLA–APP is therapeutically exploitable unknown
    • Range of FAD-linked VPS10p mutations affecting Aβ binding not systematically mapped
  13. 2015 High

    Crystal structure of the VPS10p domain revealed a ten-bladed β-propeller with a central tunnel binding Aβ and propeptide through redundant β-sheet-recognition modes; CR-cluster deletion confirmed its necessity for APP interaction; in vivo mouse models with distinct GGA- and retromer-binding mutations dissected anterograde versus retrograde sorting functions.

    Evidence X-ray crystallography; CR-cluster deletion mutagenesis; knock-in mice with GGA-binding or retromer-binding site mutations

    PMID:25525276 PMID:25643321 PMID:26377460

    Open questions at the time
    • Full-length SorLA structure not determined
    • How VPS10p tunnel accommodates larger cargoes unknown
  14. 2016 High

    SNX27 was identified as a new SorLA adaptor forming a ternary complex with APP to promote endosome-to-surface recycling; SorLA was also shown to sort the insulin receptor back to the plasma membrane in adipocytes, strengthening insulin signaling and controlling lipolysis, and to mediate polarized trafficking via AP-1-dependent basolateral/somatodendritic targeting.

    Evidence Co-IP and recycling kinetics in neurons; tissue-specific SORLA overexpression and Sorl1 KO in mice; MDCK and hippocampal neuron polarized trafficking assays

    PMID:27192064 PMID:27322061 PMID:27466343

    Open questions at the time
    • SNX27 binding site on SorLA tail not mapped
    • Whether metabolic and neuronal sorting functions use the same tail motifs unclear
  15. 2017 High

    SorLA was shown to attenuate EphA4 receptor clustering and activation, protecting against Aβ oligomer-induced synaptic toxicity, and to modulate IL-6 signaling by mediating uptake of IL-6/IL-6R in astrocytes while soluble SorLA stabilizes IL-6 for trans signaling.

    Evidence Co-IP of SORLA-EphA4, SORLA transgenic mice with LTP/behavioral tests, human AD brain analysis; astrocyte IL-6 uptake and signaling assays

    PMID:28265003 PMID:29114064

    Open questions at the time
    • Whether EphA4 attenuation is a direct trafficking or competition effect not resolved
    • In vivo neuroinflammatory consequences of SorLA-IL-6R axis unexplored
  16. 2019 High

    In cancer cells, SorLA was found to recycle endosomal HER2 to the plasma membrane; SORLA depletion diverted HER2 to lysosomes, impairing HER2-driven signaling and tumor growth, later extended to a SorLA–HER3 trimeric complex with Rab4-dependent recycling.

    Evidence Co-IP, SORLA knockdown, HER2 trafficking, in vivo tumor assays; SorLA-HER3 co-IP, Rab4 dependence, zebrafish xenograft

    PMID:31138794 PMID:33420373

    Open questions at the time
    • Whether SorLA sorting of oncogenic RTKs is mechanistically identical to APP sorting untested
    • Structural basis of SorLA–HER2/HER3 interaction unknown
  17. 2020 High

    SORL1 depletion in hiPSC-derived neurons caused early endosome enlargement independent of amyloidogenic processing, establishing endosomal dysfunction as a primary consequence of SORL1 loss; soluble SorLA was shown to bind and activate EGFR/ERK to promote neurite outgrowth.

    Evidence CRISPR SORL1-null iPSC neurons with BACE inhibitor epistasis; sSORLA-EGFR co-precipitation, ERK assays, neurite outgrowth with pharmacological inhibition

    PMID:32492427 PMID:32601248

    Open questions at the time
    • Molecular cargo driving endosome enlargement upon SORL1 loss not identified
    • Whether sSORLA-EGFR signaling is neuroprotective in vivo unknown
  18. 2021 High

    Systematic functional screening of rare SORL1 missense variants demonstrated that pathogenic variants cause ER retention, impaired maturation, and loss of endosomal trafficking, with isogenic hiPSC validation showing increased Aβ secretion, firmly establishing SORL1 loss-of-function as a monogenic AD mechanism.

    Evidence HEK293 overexpression screen of 70 variants, CRISPR-modified hiPSCs with maturation and Aβ assays

    PMID:34922638

    Open questions at the time
    • Not all variants tested at endogenous expression levels
    • Genotype-phenotype correlation for clinical severity not established
  19. 2022 High

    SORL1's role as a general neuronal sorting receptor was confirmed: SORL1 regulates trafficking and recycling of TRKB and GLUA1 in addition to APP, with loss of GLUA1 recycling impairing synaptic function; SORL1 haploinsufficiency in minipigs phenocopied APP/PSEN mutation biomarker profiles with elevated Aβ and tau preceding plaques.

    Evidence Isogenic hiPSC neurons with KO/overexpression, MEA recordings; CRISPR-Cas9 SORL1+/− Göttingen minipigs with CSF biomarkers

    PMID:35226190 PMID:36099918

    Open questions at the time
    • Full synaptic cargo repertoire of SORL1 not defined
    • Whether haploinsufficiency is sufficient for clinical AD in humans with complete penetrance unclear
  20. 2023 High

    Structural work revealed that SORL1 dimerizes via 3Fn and VPS10p domains in retromer-positive tubules to enhance APP recycling, and transcriptomic studies in SORL1-null neurons showed cell-type-specific reduction of APOE and CLU via TGF-β/SMAD signaling; retromer stabilization by TPT-260 rescued endosomal, Aβ, and tau phenotypes dose-dependently.

    Evidence X-ray crystallography of 3Fn dimer; SORL1-null iPSC neurons with RNA-seq, SMAD modulation, retromer rescue; TPT-260 pharmacological rescue in hiPSC neurons

    PMID:36652482 PMID:37611586 PMID:37949073

    Open questions at the time
    • Whether SORL1 dimerization is regulated or constitutive unknown
    • Molecular link between SORL1 loss and SMAD-dependent APOE downregulation not fully resolved
    • In vivo efficacy of retromer stabilizers for SORL1-driven AD not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the full-length SorLA structure, how SorLA selects among its diverse cargoes for distinct endosomal fates, whether retromer-stabilizing compounds rescue AD phenotypes in vivo, and the clinical penetrance of heterozygous loss-of-function variants in human populations.
  • Full-length SorLA structure not determined
  • Cargo selectivity mechanism unresolved
  • In vivo therapeutic validation of retromer stabilizers lacking
  • Penetrance of SORL1 haploinsufficiency in humans not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 6 GO:0060090 molecular adaptor activity 4 GO:0008289 lipid binding 2
Localization
GO:0005768 endosome 4 GO:0005794 Golgi apparatus 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-9609507 Protein localization 7 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-112316 Neuronal System 2
Partners
APPEGFRERBB2ERBB3GGA1ROCK2SNX27VPS26A
Complex memberships
Retromer complex (via VPS26-FANSHY interaction)SorLA-APP complexSorLA-HER2-HER3 trimeric complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 SORL1/SorLA directs trafficking of APP into recycling pathways; when SORL1 is underexpressed, APP is sorted into Aβ-generating compartments, establishing SORL1 as a regulator of APP intracellular trafficking and amyloidogenic processing. Cell-based overexpression/knockdown with APP trafficking and Aβ production assays Nature genetics High 17220890
2001 SorLA/LR11 is synthesized as a proreceptor cleaved by furin in late Golgi compartments, activating the Vps10p domain for ligand binding; the receptor binds neuropeptides, receptor-associated protein, apolipoprotein E, and lipoprotein lipase, and mediates endocytosis from the cell surface while the major pool resides in late Golgi compartments. Furin cleavage assays, ligand binding assays, cell transfection, subcellular fractionation The Journal of biological chemistry High 11294867
2002 The cytoplasmic tail of SorLA binds GGA1 and GGA2 adaptor proteins via a novel motif (ψ-ψ-X-X-φ) in the C-terminal segment, supporting a role for SorLA in Golgi-to-endosome sorting. Co-immunoprecipitation, pulldown assays, mutagenesis of cytoplasmic tail residues FEBS letters High 11821067
2006 The SorLA/APP interaction is mediated by the cluster of complement-type repeats (CR cluster) in SorLA forming a 1:1 stoichiometric complex with the carbohydrate-linked domain of APP, resulting in APP sequestration in the Golgi and protection from amyloidogenic processing. FRET-based proximity assay, surface plasmon resonance, analytical ultracentrifugation of recombinant protein fragments Biochemistry High 16489755
2007 SorLA cytoplasmic tail mediates Golgi-to-endosome transport via an acidic cluster-dileucine-like motif and a GGA-binding site; AP-1 adaptor complex is essential for SorLA transport between Golgi membranes and endosomes; SNX1 and Vps35 (retromer) are involved in retraction of SorLA from endosomes. Chimeric receptor trafficking assays, AP-1 μ1-chain-deficient cell experiments, co-immunoprecipitation Molecular and cellular biology High 17646382
2006 SorLA is a substrate for presenilin-dependent γ-secretase cleavage, preceded by metalloprotease-dependent ectodomain shedding (α-secretase-like cleavage), analogous to other γ-secretase substrates. γ-secretase inhibitor treatment, PS1/PS2 knockout cells, metalloprotease inhibitor, PMA stimulation Molecular neurodegeneration High 16930450
2000 SorLA undergoes ectodomain shedding by a metalloprotease to release a soluble form; head activator (HA) stimulates SorLA translocation from internal membranes to the cell surface, its internalization, ectodomain shedding, and synthesis; blockade of shedding decreases cell proliferation, indicating SorLA mediates mitogenic HA signaling. Antisense oligonucleotides, metalloprotease inhibitors, ligand stimulation assays, cell proliferation assays Journal of cell science Medium 11082041
2012 SorLA interacts with the retromer complex via a FANSHY sequence in its cytoplasmic domain recognized by the VPS26 subunit; this interaction is required for retrograde sorting of SorLA (and APP) from endosomes to the TGN. Mutations in the VPS26-binding site redistribute SorLA to endosomes and increase amyloidogenic APP processing despite retained APP-binding activity. Motif identification, mutagenesis, VPS26 knockdown, co-immunoprecipitation, APP processing assays The Journal of neuroscience High 22279231
2012 GGA1 specifically mediates LR11 endocytic traffic; the LR11 GGA-binding motif (when mutated) alters endosomal distribution of LR11 and its effects on APP traffic and Aβ production. GGA1 knockdown reduces both LR11- and BACE1-mediated modulation of APP processing. Mutagenesis of BACE1 S498A enhances BACE1 targeting to LR11-positive compartments and nullifies LR11-mediated Aβ reduction. siRNA knockdown, GGA-binding motif mutagenesis, APP trafficking assays, Aβ ELISA Molecular biology of the cell High 22621900
2014 SorLA directs lysosomal targeting of nascent Aβ peptides by binding Aβ to its amino-terminal VPS10P domain; overexpression of SORLA in mice decreases brain Aβ levels. A familial AD mutation in SORL1 impairs Aβ binding to the VPS10P domain, revealing loss of SorLA's Aβ-sorting function as a disease mechanism. SORLA transgenic mouse model, brain Aβ measurement, domain binding assays, familial mutation functional testing Science translational medicine High 24523320
2015 Crystal structure of the human SorLA VPS10p domain (ten-bladed β-propeller with a central tunnel) in unbound and Aβ-bound states reveals that Aβ and an internal propeptide ligand bind at the same tunnel site; SorLA VPS10p recognizes peptides in redundant modes without strict sequence dependence, favoring β-sheet-forming peptides. X-ray crystallography, structural analysis of ligand complexes Nature structural & molecular biology High 25643321
2010 ROCK2 (Rho-associated coiled-coil kinase 2) binds LR11/SorLA, co-immunoprecipitates from human brain tissue, and phosphorylates LR11 at serine 2206 in its cytoplasmic tail; ROCK2 knockdown decreases LR11 ectodomain shedding and increases intracellular LR11; S2206A mutation reduces LR11 shedding and phosphorylation and abrogates LR11-mediated Aβ reduction. LC-MS/MS kinase discovery, co-IP from brain, ROCK inhibitor treatment, siRNA knockdown, site-directed mutagenesis, in vitro phosphorylation assay The Journal of biological chemistry High 21147781
2011 SORLA prevents APP oligomerization in cultured cells and in vivo in mouse brain, eliminating the preferred oligomeric substrate for secretases and causing secretases to switch to a less efficient non-allosteric mode; secretases are allosteric enzymes requiring APP oligomerization for efficient processing. Quantitative biochemical studies combined with mathematical modeling; cell and mouse brain APP oligomerization assays The EMBO journal High 21989385
2015 The SorLA CR-cluster (11 complement-type repeat domains) is essential for interaction with APP and for protection against APP processing; deletion of the CR-cluster abolishes APP interaction and protection; mutation of CR-domain fingerprint residues changes O-linked glycosylation of APP in the Golgi. Stable cell lines expressing SorLA deletion and point mutants, co-immunoprecipitation, Western blotting, ELISA for Aβ The Journal of biological chemistry High 25525276
2015 SORLA has distinct anterograde (GGA-dependent, lysosomal targeting of Aβ) and retrograde (retromer-dependent, TGN retrieval of APP) sorting functions in vivo; disruption of retromer binding causes SORLA accumulation in endosomes, depletion from TGN, and enhanced APP processing; disruption of GGA interaction does not affect APP processing but causes increased brain Aβ levels. Mouse models expressing SORLA trafficking mutants (GGA-binding or retromer-binding site mutations), APP processing and Aβ measurement in brain The Journal of neuroscience High 26377460
2016 SNX27 binds the SORLA cytosolic tail to form a ternary complex with APP; SNX27 enhances cell-surface SORLA and APP levels and endosome-to-cell-surface recycling of APP; depletion of SNX27 reduces APP recycling in a SORLA-dependent manner; SNX27 overexpression increases non-amyloidogenic surface APP cleavage products in a SORLA-dependent manner. Co-immunoprecipitation, knockdown/overexpression, APP recycling kinetics assay, Aβ measurement The Journal of neuroscience High 27466343
2001 LR11 overexpression in cells enables binding and internalization of apolipoprotein E-rich lipoproteins (β-VLDL) with high affinity, mediates cholesteryl ester accumulation, and promotes lipid droplet formation; ApoE content of lipoproteins is a key determinant of high-affinity binding. LR11 transfection in hamster cells, ligand binding assays, lipoprotein endocytosis and degradation assays, cholesteryl ester accumulation Arteriosclerosis, thrombosis, and vascular biology High 11557679
2002 LR11 overexpression in smooth muscle cells increases migration and invasion via upregulation of cell-surface urokinase-type plasminogen activator receptor (uPAR); anti-uPA/uPAR antibodies abolish the LR11-dependent migration; LR11 decreases uPAR catabolism, increasing its cell-surface levels. LR11 cDNA transfection, migration/invasion assays, receptor-associated protein and antibody inhibition, uPAR expression analysis Circulation High 11956127
2008 LR11/SorLA deficiency in a mouse model of amyloidosis (APPswe/PS1ΔE9) significantly increases Aβ levels, exacerbates early amyloid pathology in a gene-dose-dependent manner, and increases processing of APP holo-molecule into α-, β-, and γ-secretase-derived metabolites, demonstrating that LR11 regulates APP processing and Aβ accumulation in vivo. LR11-deficient mice crossed with AD transgenic mice; Aβ measurement; amyloid pathology quantification The Journal of neuroscience High 19036982
2008 Soluble LR11 (sLR11) promotes vascular smooth muscle cell migration in an Ang II-dependent manner via activation of focal adhesion kinase/ERK/Rac1 and complex formation between uPAR and integrin αvβ3; LR11 gene disruption greatly reduces Ang II-induced SMC migration and arterial intimal thickening in mice. LR11 knockout mice, femoral artery cuff model, SMC migration assays, signaling pathway analysis by FAK/ERK/Rac1 activation, uPAR-integrin co-immunoprecipitation The Journal of clinical investigation High 18618022
2013 SorLA acts as a sorting receptor for the GDNF/GFRα1 complex, directing it from the cell surface to endosomes for lysosomal degradation of GDNF while GFRα1 recycles; SorLA/GFRα1 complex also targets RET for endocytosis but not degradation, affecting GDNF-induced neurotrophic activities; SorLA-deficient mice display elevated GDNF levels, altered dopaminergic function, hyperactivity, and reduced anxiety. SorLA knockout mouse model, GDNF/GFRα1/RET trafficking assays, lysosomal degradation assays, behavioral phenotyping Cell reports High 23333276
2014 α2A adrenergic receptor (α2AAR) activation disrupts APP interaction with SorLA in cells and mouse brain, reducing Golgi localization of APP and promoting APP distribution in endosomes and β-secretase cleavage; α2AAR genetic deficiency reduces Aβ generation and AD-related pathology. Co-immunoprecipitation of APP-SorLA complex, α2AAR knockout and agonist/antagonist treatments, APP localization by fractionation, Aβ measurement, AD mouse model Proceedings of the National Academy of Sciences of the United States of America High 25404298
2015 Soluble LR11/SorLA (sLR11) suppresses thermogenesis in adipose tissue in a cell-autonomous manner; mice lacking LR11 are protected from diet-induced obesity with increased browning of white adipose tissue; sLR11 inhibits thermogenesis via BMP/TGFβ signaling pathway and reduces Smad phosphorylation. LR11 knockout mice, diet-induced obesity model, adipocyte treatment with sLR11, Smad phosphorylation assays Nature communications High 26584636
2016 SORLA acts as a sorting factor for the insulin receptor (IR) in adipocytes, redirecting internalized IR from endosomes to the plasma membrane, thereby enhancing IR surface expression and strengthening insulin signaling; SORLA overexpression in murine adipose tissue blocks triacylglyceride hydrolysis causing excessive adiposity, while Sorl1 inactivation accelerates lipolysis and protects from diet-induced obesity. Tissue-specific SORLA overexpression, Sorl1 knockout mice, IR trafficking assays, lipolysis measurements The Journal of clinical investigation High 27322061
2017 SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1-induced EphA4 clustering and activation; SORLA transgenic mice show decreased EphA4 activation and redistribution to postsynaptic densities, with milder Aβ oligomer-induced LTP deficits and memory impairment; active EphA4 levels are elevated in human AD brains and inversely correlated with SORLA/EphA4 association. Co-immunoprecipitation of SORLA-EphA4, SORLA transgenic mice, LTP recordings, behavioral tests, human AD brain analysis The Journal of experimental medicine High 29114064
2019 SORLA co-precipitates with HER2 in cancer cells and promotes recycling of endosomal HER2 back to the plasma membrane; SORLA depletion triggers HER2 targeting to late endosomal/lysosomal compartments, impairs HER2-driven signaling and in vivo tumor growth, and disrupts lysosome function. Co-immunoprecipitation, SORLA knockdown, HER2 trafficking assays, in vivo tumor growth assays Nature communications High 31138794
2017 SorLA mediates efficient cellular uptake of IL-6 and soluble IL-6 receptor (IL-6R) in astrocytes; SorLA interacts with membrane-bound IL-6R at the cell surface and downregulates IL-6 cis signaling; soluble SorLA ectodomain (shed form) acts as an IL-6 carrier protein stabilizing IL-6 for trans signaling. SorLA-mediated uptake assays in astrocytes, IL-6 signaling assays, co-immunoprecipitation, ectodomain shedding analysis Molecular and cellular biology High 28265003
2020 SORL1 depletion in hiPSC-derived neurons causes early endosome enlargement and altered APP localization in early endosomes (a site of BACE cleavage); this endosomal phenotype is selective to neurons (not microglia) and is independent of amyloidogenic APP processing, as BACE inhibition does not rescue endosome enlargement. CRISPR-Cas9 SORL1 depletion in hiPSCs, endosome size measurement, APP localization by immunofluorescence, BACE inhibitor treatment, comparison across cell types Cell reports High 32492427
2022 SORL1 regulates endosomal trafficking and recycling of APP, TRKB, and GLUA1 in human hiPSC-derived neurons; SORL1 depletion impairs trafficking of all three cargoes to late endosomes/lysosomes and reduces recycling endosome-to-cell-surface delivery of APP and GLUA1; SORL1 overexpression enhances endosomal recycling; loss of GLUA1 recycling functionally impairs synaptic activity measured by MEA. Isogenic hiPSC SORL1 knockout/overexpression, confocal microscopy, cell surface recycling assays, lysosomal degradation assays, MEA recordings, RNA sequencing Cellular and molecular life sciences High 35226190
2014 Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 in leukocytes; CD9 colocalization with LR11 on the cell surface restrains shedding; CD9 knockdown or antibody blockade increases sLR11 release, which is abrogated by metalloprotease inhibitor GM6001. Confocal colocalization, CD9 overexpression/knockdown, neutralizing antibody, metalloprotease inhibitor, sLR11 ELISA Experimental & molecular medicine High 24699135
2010 SorCS1 (a sortilin family member) forms complexes with APP, SorL1, and Vps35 recoverable from non-transgenic mouse brain; Sorcs1 hypomorphic female mice show decreased total SorL1 (29%) and Vps35 (49%) protein levels and increased endogenous murine Aβ40 and Aβ42, indicating SorCS1 functionally interacts with SorLA/retromer in APP/Aβ metabolism. Co-immunoprecipitation from mouse brain, Sorcs1 hypomorphic mouse model, Aβ ELISA, Western blot quantification The Journal of neuroscience Medium 20881129
2012 An intronic antisense ncRNA (51A) mapping to intron 1 of SORL1 drives a splicing shift from canonical long SORL1 variant A to an alternatively spliced form, resulting in decreased SORL1 variant A synthesis and impaired APP processing leading to increased Aβ formation; 51A is upregulated in AD cerebral cortex. ncRNA overexpression, SORL1 isoform quantification, APP processing and Aβ assays, human brain expression analysis Disease models & mechanisms Medium 22996644
2021 Rare SORL1 missense variants (S114R, R332W, G543E, S577P, R654W, and others) cause impaired SorLA maturation and endosomal trafficking by retaining the protein in the endoplasmic reticulum, reducing delivery of mature SorLA to the plasma membrane and endosomal system; R332W and R654W variants expressed at endogenous levels in hiPSCs increase Aβ secretion, demonstrating loss-of-function. HEK293 overexpression screen (70 variants), CRISPR/Cas9-modified hiPSCs, maturation assays, subcellular localization by immunofluorescence, Aβ ELISA Acta neuropathologica communications High 34922638
2020 Soluble SORLA (sSORLA) binds and activates the EGF receptor (EGFR), triggering ERK activation and Fos upregulation to enhance neurite outgrowth and regeneration; pharmacological EGFR or ERK inhibition reverses sSORLA-dependent neurite outgrowth enhancement. SORLA transgenic neurons, sSORLA purification, co-precipitation of sSORLA with EGFR, EGFR phosphorylation assay, ERK activation, pharmacological inhibition, neurite outgrowth assays, RNAseq The Journal of neuroscience High 32601248
2021 SorLA interacts directly with HER3 and forms a trimeric complex with HER2 and HER3, attenuating lysosomal degradation of the HER2-HER3 dimer in a Rab4-dependent recycling manner; heregulin-mediated signaling supports SorLA transcription downstream of the MAPK pathway; SorLA loss sensitizes cancer cells to neratinib. Co-immunoprecipitation of SorLA-HER3, Rab4-dependent recycling assays, SorLA knockdown, in vivo zebrafish xenograft, MAPK pathway inhibition Oncogene High 33420373
2023 SORLA dimerizes via its fibronectin-type-III (3Fn) and VPS10p domains within retromer-positive endosomal tubules; a SORLA fragment comprising the 3Fn, transmembrane, and cytoplasmic domains forms dimers and enhances retromer-dependent recycling of APP by decreasing amyloidogenic processing. X-ray crystallography, AlphaFold structural modeling, SORLA fragment functional assays, APP processing assays Proceedings of the National Academy of Sciences of the United States of America High 36652482
2023 Loss of SORL1 in neurons (but not astrocytes) causes cell-type-specific reduction of APOE and CLU (clusterin) and altered lipid profiles; TGF-β/SMAD signaling is implicated in SORL1 function; modulating SMAD signaling alters APOE RNA levels in a SORL1-dependent manner; retromer enhancement rescues tau phenotypes but not APOE levels in SORL1-null neurons. SORL1-null iPSCs differentiated to multiple cell types, RNA sequencing, APOE/CLU quantification, retromer rescue experiments, SMAD signaling modulation Cell reports High 37611586
2022 SORL1 haploinsufficiency in Göttingen minipigs (CRISPR-Cas9 engineered) phenocopies the preclinical in vivo AD biomarker profile of APP/PSEN1/PSEN2 mutations, with elevated Aβ and tau biofluid levels preceding amyloid plaque formation, supporting SORL1 haploinsufficiency as causal for AD through endosome cytopathology. CRISPR-Cas9 minipig SORL1 haploinsufficiency model, CSF and blood Aβ/tau biomarker measurement Cell reports. Medicine High 36099918
2016 SorLA mediates polarized trafficking in neurons (somatodendritic domain) and epithelial MDCK cells (basolateral surface); polarized distribution depends on an acidic cluster motif and involves the AP-1 adaptor complex; SorLA can mediate transcytosis across tight cell layers. MDCK polarized cell trafficking, hippocampal neuron localization, AP-1 dependence, transcytosis assay The FEBS journal Medium 27192064
2013 Soluble LR11 (sLR11) regulates hypoxia-induced uPAR-mediated adhesion of hematopoietic stem and progenitor cells (HSPCs) to bone marrow stromal cells; hypoxia increases LR11 expression in HSPCs via HIF-1α binding to the LR11 promoter; lr11-/- mouse HSPCs show reduced hypoxia-enhanced attachment; sLR11 promotes HSPC adhesion through uPAR. LR11 knockout mice, HSPC adhesion assays, HIF-1α ChIP, uPAR blocking antibodies, U937 cell hypoxia experiments The Journal of biological chemistry High 23486467
2024 The SORL1 missense variant p.R953C occurs at a critical position in the YWTD-domain and causes retention of SorLA in the ER, reducing maturation, shedding, and normal endosomal trafficking, consistent with a pathogenic loss-of-function mechanism for AD. Family sequencing, SORL1 variant functional studies in cells, ER retention assays, maturation and shedding assays Acta neuropathologica Medium 38244079
2023 Pharmacological enhancement of retromer (TPT-260, a retromer-stabilizing molecule) rescues endosomal, amyloid, and tau pathologies in SORL1-deficient, haploinsufficient, and variant-expressing hiPSC-derived cortical neurons; the degree of rescue depends on the number of functional SORL1 copies, establishing the SORL1-retromer axis as therapeutically targetable. hiPSC-derived cortical neurons with SORL1 CRISPR variants, TPT-260 treatment, retromer subunit quantification, endosome, Aβ, and tau phenotype assays Stem cell reports Medium 37949073
1999 LR11 protein is localized mainly to neurons throughout the rat and human brain, with highest immunoreactivity in hippocampus, brainstem nuclei, and Purkinje cells; a unique single cytoplasmic punctum (putative botrysome) is observed near apical dendrites of pyramidal neurons, suggesting roles in intracellular trafficking. Immunohistochemistry in rat and human brain with anti-LR11 polyclonal antibody Brain research Medium 10375696

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nature genetics 925 17220890
2004 Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Archives of neurology 280 15313836
2015 Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease. JAMA neurology 237 25365775
2012 Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing. The Journal of neuroscience : the official journal of the Society for Neuroscience 221 22279231
2007 Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA. Molecular and cellular biology 164 17646382
2012 An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer's disease brain samples. Disease models & mechanisms 157 22996644
2001 Activation and functional characterization of the mosaic receptor SorLA/LR11. The Journal of biological chemistry 150 11294867
2015 Coding mutations in SORL1 and Alzheimer disease. Annals of neurology 145 25382023
2006 Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11. Biochemistry 140 16489755
2010 Diabetes-associated SorCS1 regulates Alzheimer's amyloid-beta metabolism: evidence for involvement of SorL1 and the retromer complex. The Journal of neuroscience : the official journal of the Society for Neuroscience 133 20881129
2014 Lysosomal sorting of amyloid-β by the SORLA receptor is impaired by a familial Alzheimer's disease mutation. Science translational medicine 132 24523320
2011 Meta-analysis of the association between variants in SORL1 and Alzheimer disease. Archives of neurology 132 21220680
2017 Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls. Neurobiology of aging 131 28789839
2020 Depletion of the AD Risk Gene SORL1 Selectively Impairs Neuronal Endosomal Traffic Independent of Amyloidogenic APP Processing. Cell reports 120 32492427
2008 Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: evidence for a proximal role in Alzheimer's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 109 19036982
2017 Characterization of pathogenic SORL1 genetic variants for association with Alzheimer's disease: a clinical interpretation strategy. European journal of human genetics : EJHG 106 28537274
2022 The Alzheimer's gene SORL1 is a regulator of endosomal traffic and recycling in human neurons. Cellular and molecular life sciences : CMLS 98 35226190
2013 Sorting receptor SORLA--a trafficking path to avoid Alzheimer disease. Journal of cell science 98 23813966
2002 The sorLA cytoplasmic domain interacts with GGA1 and -2 and defines minimum requirements for GGA binding. FEBS letters 97 11821067
2019 SORL1 genetic variants and Alzheimer disease risk: a literature review and meta-analysis of sequencing data. Acta neuropathologica 92 30911827
2014 The Role of SORL1 in Alzheimer's Disease. Molecular neurobiology 91 24833601
2016 A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer's disease. Acta neuropathologica 87 27026413
2007 Neuronal LR11/sorLA expression is reduced in mild cognitive impairment. Annals of neurology 84 17721864
2001 LR11, a mosaic LDL receptor family member, mediates the uptake of ApoE-rich lipoproteins in vitro. Arteriosclerosis, thrombosis, and vascular biology 81 11557679
2006 Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel gamma-secretase substrates. Molecular neurodegeneration 78 16930450
2009 Reduction of SorLA/LR11, a sorting protein limiting beta-amyloid production, in Alzheimer disease cerebrospinal fluid. Archives of neurology 76 19364929
2014 α(2A) adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction. Proceedings of the National Academy of Sciences of the United States of America 69 25404298
1999 Neuronal localization of a novel mosaic apolipoprotein E receptor, LR11, in rat and human brain. Brain research 67 10375696
1982 Transformation-dependent alterations is glycoproteins of extracellular matrix of human fibroblasts. Characterization of GP250 and the collagen-like GP140. The Journal of biological chemistry 66 6292208
2011 Quantitative modelling of amyloidogenic processing and its influence by SORLA in Alzheimer's disease. The EMBO journal 63 21989385
2000 Ectodomain shedding, translocation and synthesis of SorLA are stimulated by its ligand head activator. Journal of cell science 63 11082041
2016 Risk factor SORL1: from genetic association to functional validation in Alzheimer's disease. Acta neuropathologica 61 27638701
2019 SORLA regulates endosomal trafficking and oncogenic fitness of HER2. Nature communications 59 31138794
2016 SORL1 mutations in early- and late-onset Alzheimer disease. Neurology. Genetics 59 27822510
1999 Expression of LR11, a mosaic LDL receptor family member, is markedly increased in atherosclerotic lesions. Arteriosclerosis, thrombosis, and vascular biology 59 10559012
2017 Trafficking in Alzheimer's Disease: Modulation of APP Transport and Processing by the Transmembrane Proteins LRP1, SorLA, SorCS1c, Sortilin, and Calsyntenin. Molecular neurobiology 58 29079999
2013 SorLA controls neurotrophic activity by sorting of GDNF and its receptors GFRα1 and RET. Cell reports 56 23333276
2015 Soluble LR11/SorLA represses thermogenesis in adipose tissue and correlates with BMI in humans. Nature communications 55 26584636
2002 Enhanced expression of the LDL receptor family member LR11 increases migration of smooth muscle cells in vitro. Circulation 55 11956127
2011 Association of the Alzheimer's gene SORL1 with hippocampal volume in young, healthy adults. The American journal of psychiatry 54 21730226
2008 Ang II-stimulated migration of vascular smooth muscle cells is dependent on LR11 in mice. The Journal of clinical investigation 54 18618022
2016 SNX27 and SORLA Interact to Reduce Amyloidogenic Subcellular Distribution and Processing of Amyloid Precursor Protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 27466343
2012 GGA1-mediated endocytic traffic of LR11/SorLA alters APP intracellular distribution and amyloid-β production. Molecular biology of the cell 53 22621900
2008 Association of distinct variants in SORL1 with cerebrovascular and neurodegenerative changes related to Alzheimer disease. Archives of neurology 53 19064752
2015 Structural basis for amyloidogenic peptide recognition by sorLA. Nature structural & molecular biology 50 25643321
2009 Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain. Molecular neurodegeneration 49 19889229
2019 Regulatory Roles of Sortilin and SorLA in Immune-Related Processes. Frontiers in pharmacology 48 30666202
2016 SORLA facilitates insulin receptor signaling in adipocytes and exacerbates obesity. The Journal of clinical investigation 48 27322061
2010 Rho kinase II phosphorylation of the lipoprotein receptor LR11/SORLA alters amyloid-beta production. The Journal of biological chemistry 46 21147781
2016 Sorting receptor SORLA: cellular mechanisms and implications for disease. Cellular and molecular life sciences : CMLS 45 27832290
2009 Association of SORL1 gene variants with Alzheimer's disease. Brain research 45 19368828
2007 A secreted soluble form of LR11, specifically expressed in intimal smooth muscle cells, accelerates formation of lipid-laden macrophages. Arteriosclerosis, thrombosis, and vascular biology 45 17332490
2008 The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer's disease. Current neurology and neuroscience reports 44 18713574
2023 Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer's disease risk gene SORL1. Cell reports 43 37611586
2009 Implication of sex and SORL1 variants in italian patients with Alzheimer disease. Archives of neurology 43 19822782
2017 Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene. Acta neuropathologica communications 41 28595629
2014 ApoE-isoform-dependent cellular uptake of amyloid-β is mediated by lipoprotein receptor LR11/SorLA. Biochemical and biophysical research communications 39 25482438
2022 A genetically modified minipig model for Alzheimer's disease with SORL1 haploinsufficiency. Cell reports. Medicine 38 36099918
2017 SORLA attenuates EphA4 signaling and amyloid β-induced neurodegeneration. The Journal of experimental medicine 37 29114064
2015 Distinct Functions for Anterograde and Retrograde Sorting of SORLA in Amyloidogenic Processes in the Brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 37 26377460
2021 Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of Alzheimer's disease. Biological chemistry 36 34619027
2014 SorLA complement-type repeat domains protect the amyloid precursor protein against processing. The Journal of biological chemistry 36 25525276
2011 Impact of SORL1 single nucleotide polymorphisms on Alzheimer's disease cerebrospinal fluid markers. Dementia and geriatric cognitive disorders 36 21997402
2009 Development of an immunoassay for the quantification of soluble LR11, a circulating marker of atherosclerosis. Clinical chemistry 35 19661140
2015 Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1. Molecular neurobiology 34 26611835
2009 A study of the SORL1 gene in Alzheimer's disease and cognitive function. Journal of Alzheimer's disease : JAD 34 19584446
2009 Enhanced circulating soluble LR11 in patients with coronary organic stenosis. Atherosclerosis 34 20047743
2022 Upregulated of ANXA3, SORL1, and Neutrophils May Be Key Factors in the Progressionof Ankylosing Spondylitis. Frontiers in immunology 33 35464477
2017 Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA. Cellular and molecular life sciences : CMLS 33 28799085
2008 Intracellular trafficking of LRP9 is dependent on two acidic cluster/dileucine motifs. Histochemistry and cell biology 33 18461348
2013 The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan. Molecular psychiatry 32 24166411
2008 Identification of acidic dileucine signals in LRP9 that interact with both GGAs and AP-1/AP-2. Traffic (Copenhagen, Denmark) 31 18627575
2006 Pitavastatin attenuates the PDGF-induced LR11/uPA receptor-mediated migration of smooth muscle cells. Biochemical and biophysical research communications 29 16919601
2017 SORL1 Variants Show Different Association with Early-Onset and Late-Onset Alzheimer's Disease Risk. Journal of Alzheimer's disease : JAD 27 28527213
2015 Y682G Mutation of Amyloid Precursor Protein Promotes Endo-Lysosomal Dysfunction by Disrupting APP-SorLA Interaction. Frontiers in cellular neuroscience 27 25904844
2020 Brain transcriptome analysis reveals subtle effects on mitochondrial function and iron homeostasis of mutations in the SORL1 gene implicated in early onset familial Alzheimer's disease. Molecular brain 26 33076949
2016 SORL1 gene, plasma biomarkers, and the risk of Alzheimer's disease for the Han Chinese population in Taiwan. Alzheimer's research & therapy 26 28034305
2014 Influence of genetic variants in SORL1 gene on the manifestation of Alzheimer's disease. Neurobiology of aging 26 25659857
2021 Impaired SorLA maturation and trafficking as a new mechanism for SORL1 missense variants in Alzheimer disease. Acta neuropathologica communications 25 34922638
2012 SORL1 genetic variants and cerebrospinal fluid biomarkers of Alzheimer’s disease. European archives of psychiatry and clinical neuroscience 25 22286501
2014 Tetraspanin CD9 modulates ADAM17-mediated shedding of LR11 in leukocytes. Experimental & molecular medicine 23 24699135
2012 Interrelations between CSF soluble AβPPβ, amyloid-β 1-42, SORL1, and tau levels in Alzheimer's disease. Journal of Alzheimer's disease : JAD 23 22045485
2012 Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias. Clinica chimica acta; international journal of clinical chemistry 23 22750733
1998 Developmental regulation of LR11 expression in murine brain. DNA and cell biology 23 9726247
2013 The soluble form of LR11 protein is a regulator of hypoxia-induced, urokinase-type plasminogen activator receptor (uPAR)-mediated adhesion of immature hematological cells. The Journal of biological chemistry 22 23486467
2013 An updated meta-analysis of the association between SORL1 variants and the risk for sporadic Alzheimer's disease. Journal of Alzheimer's disease : JAD 22 23948893
2009 Calnuc binds to LRP9 and affects its endosomal sorting. Traffic (Copenhagen, Denmark) 22 19497050
2021 A feed-forward loop between SorLA and HER3 determines heregulin response and neratinib resistance. Oncogene 21 33420373
2020 Soluble SORLA Enhances Neurite Outgrowth and Regeneration through Activation of the EGF Receptor/ERK Signaling Axis. The Journal of neuroscience : the official journal of the Society for Neuroscience 21 32601248
2012 Sortilin and SorLA regulate neuronal sorting of trophic and dementia-linked proteins. Molecular neurobiology 21 22297619
2009 Sequence variation in SORL1 and dementia risk in Swedes. Neurogenetics 21 19653016
2012 Increased circulating soluble LR11 in patients with acute coronary syndrome. Clinica chimica acta; international journal of clinical chemistry 20 23127357
2017 SorLA in Interleukin-6 Signaling and Turnover. Molecular and cellular biology 19 28265003
2024 A familial missense variant in the Alzheimer's disease gene SORL1 impairs its maturation and endosomal sorting. Acta neuropathologica 18 38244079
2023 Dimerization of the Alzheimer's disease pathogenic receptor SORLA regulates its association with retromer. Proceedings of the National Academy of Sciences of the United States of America 18 36652482
2016 Levels of soluble LR11/SorLA are highly increased in the bile of patients with biliary tract and pancreatic cancers. Clinica chimica acta; international journal of clinical chemistry 18 27079357
2016 Sex-specific characterization and evaluation of the Alzheimer's disease genetic risk factor sorl1 in zebrafish during aging and in the adult brain following a 100 ppb embryonic lead exposure. Journal of applied toxicology : JAT 18 27535807
2000 Differential expression of LR11 during proliferation and differentiation of cultured neuroblastoma cells. Biochemical and biophysical research communications 18 10964672
2023 Pharmacologic enhancement of retromer rescues endosomal pathology induced by defects in the Alzheimer's gene SORL1. Stem cell reports 17 37949073
2016 Polarized trafficking of the sorting receptor SorLA in neurons and MDCK cells. The FEBS journal 17 27192064