Affinage

AIPL1

Aryl-hydrocarbon-interacting protein-like 1 · UniProt Q9NZN9

Length
384 aa
Mass
43.9 kDa
Annotated
2026-04-28
67 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AIPL1 is a photoreceptor-specific co-chaperone essential for the biosynthesis, assembly, and stability of the rod and cone cGMP phosphodiesterase (PDE6) holoenzyme, and its loss causes Leber congenital amaurosis (LCA) through rapid PDE6 degradation and photoreceptor degeneration (PMID:15365178, PMID:20042464). AIPL1 engages HSP90 in its closed conformation via its TPR domain and a helix-7 extension, while its FKBP-like domain—structurally characterized by crystallography and cryo-EM—binds the farnesyl moiety of the PDE6α subunit through a W72 flip-out switch, positioning AIPL1 as a bridge between chaperone machinery and client (PMID:28739921, PMID:36657440, PMID:28973376). In the absence of AIPL1, newly synthesized PDE6 subunits are rapidly degraded by the proteasome; in rods this causes cGMP elevation, whereas in cones the guanylate cyclase RetGC1 is also destabilized, leading to cGMP depletion and a distinct death mechanism (PMID:19758987, PMID:24108108). The C-terminal proline-rich domain confers autonomous chaperone activity for binding non-native proteins and negatively regulates AIPL1–HSP90 affinity, while the FKBP domain lacks canonical peptidyl-prolyl isomerase activity (PMID:23418749).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Establishing where AIPL1 acts: immunohistochemistry showed AIPL1 is confined to rod photoreceptors in the adult human retina, restricting its functional context to a single cell type.

    Evidence Immunohistochemistry with validated antibody on human retinal sections

    PMID:11929855

    Open questions at the time
    • Does not address developmental expression in cones
    • Does not identify AIPL1's molecular partners or substrates
  2. 2003 High

    Two key properties were defined: AIPL1 selectively binds farnesylated proteins, and it is expressed in both rods and cones during fetal retinal development, explaining why LCA affects both photoreceptor types despite adult rod restriction.

    Evidence Yeast two-hybrid and cell-based farnesylation assay; immunohistochemistry with cone markers on fetal human retina

    PMID:14555765 PMID:14638743

    Open questions at the time
    • The physiological farnesylated substrate in vivo was not yet identified
    • Whether developmental cone expression is functionally required was untested
  3. 2004 High

    Knockout and hypomorphic mouse models demonstrated that AIPL1 is specifically required for PDE6 stability in a dose-dependent manner; its loss ablates PDE6, elevates cGMP, and causes rapid photoreceptor degeneration, while other phototransduction proteins remain unaffected.

    Evidence Aipl1 knockout and hypomorphic mice; western blot, cGMP assays, ERG

    PMID:15365173 PMID:15365178

    Open questions at the time
    • Direct physical interaction with PDE6 was not shown
    • Whether the mechanism involves HSP90 co-chaperoning was unknown
    • Cone-autonomous requirement not yet tested
  4. 2004 Medium

    AIPL1 was found to interact with the NEDD8/ubiquitin-like modifier regulator NUB1 and to modulate NUB1 subcellular localization in a chaperone-like fashion; disease-causing mutations disrupted this interaction.

    Evidence Yeast two-hybrid, co-IP, deletion mapping, immunofluorescence in transfected cells

    PMID:12374762 PMID:15081406 PMID:15347646

    Open questions at the time
    • Physiological relevance of NUB1 interaction in photoreceptors was not demonstrated
    • Whether NUB1 binding is independent of PDE6 chaperoning is unclear
  5. 2008 High

    AIPL1 was shown to interact with HSP90 and HSP70 through its TPR domain, establishing it as a co-chaperone; LCA mutations compromised these interactions, and AIPL1 cooperated with HSP70 to suppress protein aggregation.

    Evidence Yeast two-hybrid, co-IP, in vitro aggregation suppression, mutagenesis

    PMID:18408180

    Open questions at the time
    • Whether HSP90 or HSP70 cooperation is relevant for PDE6 folding in vivo was untested
    • No structural information on the AIPL1–HSP90 interface
  6. 2009 High

    Direct interaction between AIPL1 and the PDE6α catalytic subunit was demonstrated, and pulse-chase experiments showed that without AIPL1, newly synthesized PDE6 subunits are rapidly degraded by the proteasome, establishing AIPL1 as essential for PDE6 holoenzyme assembly rather than just stability.

    Evidence Co-IP with monoclonal antibody, pulse-chase, proteasome inhibitor experiments in Aipl1−/− retinas

    PMID:19758987

    Open questions at the time
    • Stoichiometry of the AIPL1–PDE6 complex unknown
    • Whether AIPL1 acts co-translationally or post-translationally was not resolved
  7. 2009 High

    Cell-type-specific rescue proved that AIPL1 is required autonomously within cone photoreceptors for cone PDE6 stability and cone survival, not merely through a secondary rod-driven effect.

    Evidence Rod-specific transgenic rescue of Aipl1−/− mice with ERG and immunohistochemistry

    PMID:20042464

    Open questions at the time
    • Molecular basis for any difference between rod and cone PDE6 chaperoning was unknown
  8. 2013 High

    Cone-specific Aipl1 ablation revealed a mechanistically distinct cone death pathway: loss of cone PDE6 is accompanied by dramatic reduction of guanylate cyclase RetGC1 and decreased (not elevated) cGMP, contrasting the rod phenotype.

    Evidence Cone-specific Aipl1 knockout mouse, cGMP quantification, western blot, immunohistochemistry

    PMID:24108108

    Open questions at the time
    • Whether AIPL1 directly chaperones RetGC1 or the effect is indirect was unresolved
    • Mechanism of RetGC1 destabilization in cones was not determined
  9. 2013 High

    Biochemical dissection showed the C-terminal proline-rich domain (PRD) is the autonomous chaperone module required for binding non-native proteins, and that it negatively regulates HSP90 affinity; the FKBP domain was confirmed to lack peptidyl-prolyl isomerase activity.

    Evidence In vitro aggregation suppression, domain truncation, PPIase activity assay

    PMID:23418749

    Open questions at the time
    • Whether the PRD contacts PDE6 directly during chaperoning was unknown
    • No in vivo validation of PRD-only truncation effects
  10. 2017 High

    Crystal structures of the AIPL1 FKBP domain revealed a unique prenyl-binding pocket controlled by a W72 flip-out switch, and showed that the LCA-causing V71F mutation locks the pocket in a closed, prenyl-incompatible conformation—providing the first atomic-level explanation of disease pathogenesis.

    Evidence X-ray crystallography, NMR, molecular dynamics, mutagenesis

    PMID:28739921

    Open questions at the time
    • Structure of the full-length AIPL1–PDE6 complex was not available
    • Contribution of FKBP domain to HSP90 binding was not structurally resolved
  11. 2017 High

    Functional assays confirmed that both the FKBP and TPR domains are indispensable for HSP90 binding and PDE6 catalytic activation; the FKBP domain specifically recognizes the PDE6α farnesyl moiety, while LCA mutations in either domain ablate function.

    Evidence Co-IP, domain deletion, heterologous PDE6 expression, cGMP activity assay

    PMID:28973376

    Open questions at the time
    • Whether AIPL1 catalytically cycles on and off PDE6 was unknown
    • Role of the N-terminal region was not addressed
  12. 2022 High

    AIPL1 binds HSP90 in its closed state with 1:2 stoichiometry; unexpectedly, AIPL1 can mature unprenylated cone PDE6C, and a mouse with unfarnesylated PDE6A retains normal PDE6 expression, demonstrating that prenyl recognition is not strictly required for chaperoning.

    Evidence Binding assays, heterologous PDE6 expression, Aipl1−/− rescue with unprenylatable PDE6A in mice

    PMID:35065964

    Open questions at the time
    • If farnesyl binding is dispensable, its precise role in substrate recognition requires reinterpretation
    • Structural basis of the closed-HSP90 preference was not yet resolved
  13. 2023 High

    Cryo-EM at 3.9 Å resolution revealed that the AIPL1 FKBP domain contacts the HSP90 dimer interface while the N-terminus inserts into the HSP90 lumen like a client, and the TPR domain undergoes large swing motions; deletion of seven N-terminal residues impaired co-chaperone function.

    Evidence Cryo-EM, crosslinking mass spectrometry, multi-body refinement, N-terminal deletion mutagenesis

    PMID:36657440

    Open questions at the time
    • Structure of AIPL1 bound simultaneously to HSP90 and PDE6 substrate is not available
    • Dynamics of client hand-off from AIPL1 to PDE6 assembly intermediates remain unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A ternary complex structure of AIPL1–HSP90–PDE6 is needed to define how the co-chaperone hands off the client; the mechanism by which AIPL1 loss destabilizes RetGC1 specifically in cones, and whether AIPL1 interactions with NUB1/FAT10 and EB1/EB3 play physiological roles in photoreceptors, remain open questions.
  • No ternary AIPL1–HSP90–PDE6 structure exists
  • RetGC1 destabilization mechanism in cones is uncharacterized
  • In vivo relevance of NUB1, FAT10, and EB1/EB3 interactions for photoreceptor function is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 6 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005929 cilium 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-9709957 Sensory Perception 5 R-HSA-1643685 Disease 4
Partners
HSP90AA1HSPA1AMAPRE1MAPRE3NUB1PDE6APDE6CUBD
Complex memberships
AIPL1–HSP90 co-chaperone complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 AIPL1 interacts specifically with farnesylated proteins via yeast two-hybrid screen, and enhances the processing of farnesylated proteins in cultured human cells; LCA-causing mutations in AIPL1 compromise this interaction. Yeast two-hybrid screen, cell-based farnesylation assay Proceedings of the National Academy of Sciences of the United States of America High 14555765
2004 AIPL1 knockout mice lack rod cGMP phosphodiesterase (PDE6) and have elevated cGMP levels prior to photoreceptor degeneration, demonstrating that AIPL1 is required for the stability of farnesylated rod PDE6. Knockout mouse model, biochemical assay of PDE6 levels and cGMP Proceedings of the National Academy of Sciences of the United States of America High 15365178
2004 AIPL1 knockdown in mice causes a reduction in rod cGMP phosphodiesterase (PDE6) proportional to the decrease in AIPL1, while other photoreceptor proteins are unaffected, establishing AIPL1 as a specialized chaperone required for rod PDE6 biosynthesis. Hypomorphic mouse model, western blot quantification of PDE6, single-cell and ERG electrophysiology Proceedings of the National Academy of Sciences of the United States of America High 15365173
2002 AIPL1 protein is localized exclusively in rod photoreceptors (inner segments, nuclei, and synaptic spherules) of the adult human retina, not in cone photoreceptors, as determined by immunohistochemistry with a validated antibody. Immunohistochemistry, western blot of human retinal extracts Human molecular genetics High 11929855
2002 AIPL1 interacts with the cell cycle regulator NUB1 (NEDD8 Ultimate Buster 1) as identified by yeast two-hybrid screen and confirmed by co-immunoprecipitation in Y79 retinoblastoma cells. Yeast two-hybrid, co-immunoprecipitation Human molecular genetics Medium 12374762
2004 AIPL1 modulates the nuclear translocation of NUB1, shifting NUB1 distribution toward the cytoplasm upon co-transfection, and suppresses inclusion formation by NUB1 fragments in a chaperone-like manner; this function requires the C-terminal region of AIPL1. Co-transfection, immunofluorescence microscopy, deletion mutagenesis The Journal of biological chemistry Medium 15347646
2008 AIPL1 interacts with the molecular chaperones Hsp90 and Hsp70 through its TPR domain; LCA-causing mutations in AIPL1 compromise these interactions; AIPL1 cooperates with Hsp70 (but not Hsp90) to suppress NUB1 fragment aggregation. Yeast two-hybrid, co-immunoprecipitation, in vitro aggregation suppression assay, mutagenesis Investigative ophthalmology & visual science High 18408180
2009 AIPL1 directly interacts with the catalytic alpha-subunit of rod PDE6, as shown by co-immunoprecipitation with a novel monoclonal antibody; in the absence of AIPL1, newly synthesized PDE6 subunits are rapidly degraded by proteasomes due to failure of proper PDE6 holoenzyme assembly. Co-immunoprecipitation, ex vivo pulse label and pulse-chase analysis, proteasome inhibitor experiments The Journal of biological chemistry High 19758987
2009 AIPL1 is required directly in cone photoreceptors for cone PDE6 stability and cone function; transgenic rescue of AIPL1 only in rods restores rod function but leaves cone PDE6 highly reduced and cones non-functional and degenerating. Rod-specific transgenic rescue in Aipl1-/- mice, ERG, immunohistochemistry, western blot Human molecular genetics High 20042464
2013 In an all-cone mouse model lacking Aipl1, cone PDE6 stability, assembly, and membrane association are lost; additionally, the guanylate cyclase RetGC1 is dramatically reduced and cGMP levels are decreased in cones—contrasting with the cGMP elevation seen in rods lacking AIPL1, revealing mechanistic differences between rod and cone death. Cone-specific Aipl1 knockout mouse model, immunohistochemistry, western blot, cGMP measurement Human molecular genetics High 24108108
2013 The unique C-terminal proline-rich domain (PRD) of AIPL1 is required for chaperone activity (binding non-native proteins and suppressing their aggregation); truncation of the PRD severely impairs non-native protein binding. The FKBP domain of AIPL1 is enzymatically inactive as a PPIase, unlike other FKBPs. The PRD also decreases AIPL1 affinity for Hsp90, acting as a negative regulator of the Hsp90 interaction. In vitro aggregation suppression assay, domain truncation mutagenesis, binding assays Biochemistry High 23418749
2017 Crystal structures of the AIPL1-FKBP domain in apo form and in complex with isoprenyl (farnesyl) moieties reveal a unique lipid-binding module: a 'loop-out' conformation of the β4-α1 loop and a 'flip-out' switch of W72 enable prenyl binding. A second conformation (W72 flipped into the binding pocket, incapable of prenyl binding) is revealed by NMR and underlies the pathogenicity of the V71F mutant. X-ray crystallography, NMR, molecular dynamics simulation, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 28739921
2017 Both the FKBP-like domain and the TPR domain of AIPL1 are required for interaction with HSP90 and for modulating rod PDE6 catalytic activity; the FKBP-like domain binds the farnesylated PDE6α subunit through direct interaction with the farnesyl moiety; LCA-causing mutations in either domain impair HSP90 binding and fail to promote HSP90-dependent stabilization of PDE6α. Co-immunoprecipitation, domain deletion/mutagenesis, heterologous PDE6 expression system, cGMP activity assay Human molecular genetics High 28973376
2022 AIPL1 preferentially binds HSP90 in the closed state with 1:2 stoichiometry; the TPR domain and TPR helix 7 extension are the main contributors to the AIPL1/HSP90 interface; AIPL1 can induce maturation of unprenylated cone PDE6C, demonstrating that sequestration of prenyl modifications is not strictly required for PDE6 maturation; a mouse model with unfarnesylated PDE6A showed normal PDE6 expression and trafficking. Biochemical binding assays, mutagenesis, heterologous PDE6 expression, mouse model with unfarnesylated PDE6A The Journal of biological chemistry High 35065964
2023 Cryo-EM structure of the AIPL1/HSP90 complex at 3.9 Å resolution reveals that the FKBP-like domain of AIPL1 contacts the HSP90 dimer interface; the N-terminus of AIPL1 inserts into the HSP90 lumen similarly to HSP90 clients; the TPR domain undergoes large swing-like movements. Deletion of the 7 N-terminal residues of AIPL1 decreased its ability to cochaperone PDE6. Cryo-EM, crosslinking mass spectrometry, multi-body refinement, deletion mutagenesis Structure High 36657440
2003 AIPL1 is expressed in both rod and cone photoreceptors of the developing human retina (detected from 11.8 fetal weeks), following the centroperipheral gradient of photoreceptor development, explaining why both rod and cone function are affected in LCA despite AIPL1 being rod-restricted in adult human retina. Immunohistochemistry, immunofluorescence confocal microscopy with cone-specific markers Investigative ophthalmology & visual science Medium 14638743
2004 Some LCA-associated AIPL1 mutants (W278X and A336Δ2) form aggresome-like cytoplasmic particles that are ubiquitinated, indicating proteasomal targeting of misfolded AIPL1; wild-type AIPL1 distributes throughout nucleus and cytoplasm. Other mutants alter secondary structure composition or reduce thermostability without causing insolubility. Immunofluorescence microscopy in transfected cells, circular dichroism spectroscopy, thermostability assay Biochimica et biophysica acta Medium 15469903
2004 The NUB1-binding site on AIPL1 maps to residues 181–330; several LCA-associated mutations at this site abolish the AIPL1–NUB1 interaction in multiple assays. Deletion mapping, co-immunoprecipitation, GST pulldown, yeast two-hybrid Biochemical and biophysical research communications Medium 15081406
2012 AIPL1 binds non-covalently to free FAT10 and FAT10-conjugated proteins and forms a ternary complex with FAT10 and NUB1; AIPL1 antagonizes NUB1-mediated proteasomal degradation of FAT10 conjugates; AIPL1 also co-immunoprecipitates the FAT10 E1 activating enzyme UBA6. Co-immunoprecipitation, protein stability assay, pulldown PloS one Medium 22347407
2015 AIPL1 interacts with microtubule end-binding proteins EB1 and EB3; both AIPL1 and EB1/EB3 co-localize at the connecting cilia of retinal photoreceptor cells (confirmed by cryo-immunogold EM); LCA-causing mutations A197P, C239R, and W278X in AIPL1 severely compromise the EB1 interaction. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence confocal microscopy, cryo-immunogold electron microscopy PloS one Medium 25799540
2006 In rods with reduced AIPL1 levels, PDE activity is reduced while other phototransduction proteins (rhodopsin kinase, guanylate cyclase) remain normal; AIPL1 deficiency delays the photoresponse, reduces amplification, slows recovery, and limits light-induced calcium decreases—effects not fully explained by reduced PDE alone, suggesting AIPL1 affects multiple components of phototransduction. Single-cell recordings, ERG, biochemical activity assays, fluorescent calcium dye imaging in mouse rods Investigative ophthalmology & visual science Medium 16639031
2020 Retinal organoids derived from a patient carrying the C89R AIPL1 mutation show reduced levels of mutant AIPL1 protein and correspondingly reduced PDE6, corroborating the chaperone-substrate relationship in a human cellular model. hiPSC-derived retinal organoids, western blot Scientific reports Medium 32214115
2020 The AIPL1 p.G122R variant is a hypomorphic allele: it retains HSP90 binding but impairs modulation of PDE6 cGMP levels; variants in the proline-rich domain do not impair HSP90 interaction or PDE6 activity (except p.A352_P355del associated with dominant CORD). Nonsense and missense variants in FKBP-like and TPR domains abolish HSP90 interaction and PDE6 activity. In vitro co-immunoprecipitation, cGMP phosphodiesterase activity assay, mutagenesis Scientific reports High 33067476
2017 Zebrafish aipl1b (cone-specific) mutant (gosh) shows cone degeneration and markedly decreased cone PDE6 (Pde6c) and cone guanylate cyclase (zGc3); genetic interaction between aipl1b and pde6c mutations is demonstrated; zGc3 knockdown reduces Pde6c, revealing interdependence of cGMP metabolism regulators. Zebrafish mutant analysis, genetic epistasis, morpholino knockdown, immunohistochemistry Scientific reports Medium 28378769

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase. Proceedings of the National Academy of Sciences of the United States of America 146 15365178
2000 Prevalence of AIPL1 mutations in inherited retinal degenerative disease. Molecular genetics and metabolism 138 10873396
2009 Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations. Gene therapy 104 19710705
2009 Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors. Human molecular genetics 97 19299492
2004 AIPL1, the protein that is defective in Leber congenital amaurosis, is essential for the biosynthesis of retinal rod cGMP phosphodiesterase. Proceedings of the National Academy of Sciences of the United States of America 97 15365173
2004 The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations. Archives of ophthalmology (Chicago, Ill. : 1960) 84 15249368
2005 Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. Journal of medical genetics 76 16272259
2003 AIPL1, a protein implicated in Leber's congenital amaurosis, interacts with and aids in processing of farnesylated proteins. Proceedings of the National Academy of Sciences of the United States of America 66 14555765
2008 The Leber congenital amaurosis protein AIPL1 functions as part of a chaperone heterocomplex. Investigative ophthalmology & visual science 64 18408180
2002 The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina. Human molecular genetics 61 11929855
2009 AIPL1, a protein associated with childhood blindness, interacts with alpha-subunit of rod phosphodiesterase (PDE6) and is essential for its proper assembly. The Journal of biological chemistry 59 19758987
2009 The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells. Human molecular genetics 58 20042464
2011 Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining. Investigative ophthalmology & visual science 57 20702822
2002 The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1. Human molecular genetics 51 12374762
2000 A novel locus for Leber congenital amaurosis (LCA4) with anterior keratoconus mapping to chromosome 17p13. Investigative ophthalmology & visual science 50 10711674
2020 Retinal Organoids derived from hiPSCs of an AIPL1-LCA Patient Maintain Cytoarchitecture despite Reduced levels of Mutant AIPL1. Scientific reports 46 32214115
2003 The expression of the Leber congenital amaurosis protein AIPL1 coincides with rod and cone photoreceptor development. Investigative ophthalmology & visual science 42 14638743
2011 Evaluation of Italian patients with leber congenital amaurosis due to AIPL1 mutations highlights the potential applicability of gene therapy. Investigative ophthalmology & visual science 40 21474771
2016 Whole genome sequencing in cats, identifies new models for blindness in AIPL1 and somite segmentation in HES7. BMC genomics 37 27030474
2004 Retinal degeneration in Aipl1-deficient mice: a new genetic model of Leber congenital amaurosis. Brain research. Molecular brain research 37 15582159
2001 Leber's congenital amaurosis with anterior keratoconus in Pakistani families is caused by the Trp278X mutation in the AIPL1 gene on 17p. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie 31 11548141
2012 Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease causation, clinical findings, and implications for gene therapy. PloS one 29 22412862
2011 Residual electroretinograms in young Leber congenital amaurosis patients with mutations of AIPL1. Investigative ophthalmology & visual science 28 21900377
2004 The Leber congenital amaurosis protein AIPL1 modulates the nuclear translocation of NUB1 and suppresses inclusion formation by NUB1 fragments. The Journal of biological chemistry 27 15347646
2017 AIPL1: A specialized chaperone for the phototransduction effector. Cellular signalling 26 28939106
2014 Early alteration of retinal neurons in Aipl1-/- animals. Investigative ophthalmology & visual science 26 24736053
2022 Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis. Stem cell reports 25 36084639
2013 AIPL1, A protein linked to blindness, is essential for the stability of enzymes mediating cGMP metabolism in cone photoreceptor cells. Human molecular genetics 24 24108108
2003 An unusual retinal vascular morphology in connection with a novel AIPL1 mutation in Leber's congenital amaurosis. The British journal of ophthalmology 21 12881340
2020 Clinical and functional analyses of AIPL1 variants reveal mechanisms of pathogenicity linked to different forms of retinal degeneration. Scientific reports 19 33067476
2017 The integrity and organization of the human AIPL1 functional domains is critical for its role as a HSP90-dependent co-chaperone for rod PDE6. Human molecular genetics 19 28973376
2017 Aipl1 is required for cone photoreceptor function and survival through the stability of Pde6c and Gc3 in zebrafish. Scientific reports 18 28378769
2013 Unique proline-rich domain regulates the chaperone function of AIPL1. Biochemistry 18 23418749
2006 Effects of low AIPL1 expression on phototransduction in rods. Investigative ophthalmology & visual science 17 16639031
2023 Retinal Organoids from an AIPL1 CRISPR/Cas9 Knockout Cell Line Successfully Recapitulate the Molecular Features of LCA4 Disease. International journal of molecular sciences 16 36982987
2017 Unique structural features of the AIPL1-FKBP domain that support prenyl lipid binding and underlie protein malfunction in blindness. Proceedings of the National Academy of Sciences of the United States of America 16 28739921
2004 Abolished interaction of NUB1 with mutant AIPL1 involved in Leber congenital amaurosis. Biochemical and biophysical research communications 16 15081406
2001 Comparative analysis of aryl-hydrocarbon receptor interacting protein-like 1 (Aipl1), a gene associated with inherited retinal disease in humans. Mammalian genome : official journal of the International Mammalian Genome Society 16 11420621
2012 The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway. PloS one 15 22347407
2024 Effective AAV-mediated gene replacement therapy in retinal organoids modeling AIPL1-associated LCA4. Molecular therapy. Nucleic acids 14 38439910
2014 Viral-mediated vision rescue of a novel AIPL1 cone-rod dystrophy model. Human molecular genetics 14 25274777
2018 The Leber Congenital Amaurosis-Linked Protein AIPL1 and Its Critical Role in Photoreceptors. Advances in experimental medicine and biology 13 29721967
2014 AIPL1 protein and its indispensable role in cone photoreceptor function and survival. Advances in experimental medicine and biology 13 24664679
2015 Investigation of Aberrant Splicing Induced by AIPL1 Variations as a Cause of Leber Congenital Amaurosis. Investigative ophthalmology & visual science 12 26650897
2025 Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study. Lancet (London, England) 11 39986747
2023 Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1. Structure (London, England : 1993) 10 36657440
2014 AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration. Molecular vision 10 24426771
2017 NMR resonance assignments of the FKBP domain of human aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) in complex with a farnesyl ligand. Biomolecular NMR assignments 9 28236226
2014 Genome-wide homozygosity mapping in families with leber congenital amaurosis identifies mutations in AIPL1 and RDH12 genes. DNA and cell biology 9 25148430
2022 Molecular insights into the maturation of phosphodiesterase 6 by the specialized chaperone complex of HSP90 with AIPL1. The Journal of biological chemistry 8 35065964
2004 Purification, characterisation and intracellular localisation of aryl hydrocarbon interacting protein-like 1 (AIPL1) and effects of mutations associated with inherited retinal dystrophies. Biochimica et biophysica acta 8 15469903
2024 Clinical and Molecular Characterization of AIPL1-Associated Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy. American journal of ophthalmology 7 38880373
2015 The Leber congenital amaurosis protein AIPL1 and EB proteins co-localize at the photoreceptor cilium. PloS one 6 25799540
2018 NMR resonance assignments of the TPR domain of human aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1). Biomolecular NMR assignments 5 30341566
2004 Role of AIP and its homologue the blindness-associated protein AIPL1 in regulating client protein nuclear translocation. Biochemical Society transactions 5 15270697
2025 Human cone photoreceptor transplantation stimulates remodeling and restores function in AIPL1 model of end-stage Leber congenital amaurosis. Stem cell reports 4 40154478
2023 RNA-Seq Analysis of Trans-Differentiated ARPE-19 Cells Transduced by AAV9-AIPL1 Vectors. International journal of molecular sciences 3 38203368
2022 ZP3 and AIPL1 participate in GVBD of mouse oocytes by affecting the nuclear membrane localization and maturation of farnesylated prelamin A. Zygote (Cambridge, England) 3 36533678
2019 A Novel AIPL1 Nonsense Mutation: Case Report of Three Siblings Diagnosed with Leber Congenital Amaurosis. Fetal and pediatric pathology 3 31342828
2019 Gene and Cell Therapy for AIPL1-Associated Leber Congenital Amaurosis: Challenges and Prospects. Advances in experimental medicine and biology 3 31884595
2018 Generation of a human iPSC line from a patient with Leber congenital amaurosis caused by mutation in AIPL1. Stem cell research 3 30366342
2013 Structural studies on AIPL1 and its functional interactions with NUB1 to identify key interacting residues in LCA4. Journal of ocular biology, diseases, and informatics 3 24596939
2019 [Identification of AIPL1 gene variants in two Chinese families with Cone-rod dystrophy]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2 31703130
2025 Computational Evidence for Digenic Contribution of AIPL1 and BBS2 Rare Variants in Inherited Retinal Dystrophy. International journal of molecular sciences 1 41096698
2019 A new novel nonsense mutation in AIPL1 in a LCA4 family. Ophthalmic genetics 1 31576779
2025 Neural Network Prediction of Keratoconus in AIPL1-Linked Leber Congenital Amaurosis: A Proof-of-Concept Pilot Study. Journal of clinical medicine 0 41010702
2025 Restoring Sight: The Journey of AIPL1 from Discovery to Therapy. International journal of molecular sciences 0 41465493