Affinage

AIPL1

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

Length
384 aa
Mass
43.9 kDa
Annotated
2026-06-09
67 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

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 cGMP phosphodiesterase PDE6, the effector enzyme of phototransduction (PMID:15365178, PMID:15365173, PMID:19758987). It operates as a specialized client adaptor within an HSP90 chaperone heterocomplex: its FKBP-like domain recognizes the farnesyl/prenyl moiety carried on the catalytic PDE6α subunit through a unique prenyl-binding module gated by a conformational 'flip' of W72, while its TPR domain docks onto the HSP90 dimer at a 1:2 AIPL1:HSP90 stoichiometry (PMID:19758987, PMID:28739921, PMID:28973376, PMID:35065964, PMID:36657440). Both domains are required for HSP90 binding and for productive maturation of catalytically active PDE6, and the AIPL1 N-terminus inserts into the HSP90 lumen to support cochaperone function (PMID:28973376, PMID:35065964, PMID:36657440). In the absence of AIPL1, newly synthesized PDE6 subunits are not under-produced but are instead rapidly cleared by the proteasome, so that rod PDE6 is lost and cGMP accumulates prior to photoreceptor degeneration (PMID:15365178, PMID:15365173, PMID:19758987). AIPL1 is independently required in cones, where its loss destabilizes cone PDE6 and additionally depletes RetGC1 guanylate cyclase, lowering cGMP—a mechanistic contrast to the cGMP elevation seen in rods—a requirement conserved for cone PDE6c and guanylate cyclase in zebrafish (PMID:20042464, PMID:24108108, PMID:28378769). Beyond PDE6, AIPL1 binds the ubiquitin-like regulators NUB1 and FAT10, modulating NUB1 localization and antagonizing NUB1-mediated proteasomal degradation of FAT10 conjugates, and it localizes with EB1/EB3 at the photoreceptor connecting cilium (PMID:12374762, PMID:15347646, PMID:22347407, PMID:25799540). AIPL1 mutations cause Leber congenital amaurosis, and disease alleles map to and disrupt the prenyl-binding, HSP90-interacting, and NUB1/EB-binding functions of the protein (PMID:15365178, PMID:15365173, PMID:15081406, PMID:28739921, PMID:25799540, PMID:33067476).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 Medium

    Before any biochemical function was known, defining AIPL1's expression and first binding partner placed it in photoreceptors and linked it to the ubiquitin/NEDD8 regulatory machinery.

    Evidence Immunohistochemistry localizing AIPL1 to rod photoreceptors and yeast two-hybrid/Co-IP identifying NUB1

    PMID:11929855 PMID:12374762

    Open questions at the time
    • Functional consequence of the NUB1 interaction not defined
    • Did not explain the link between AIPL1 and a phototransduction phenotype
  2. 2003 Medium

    Establishing that AIPL1 binds farnesylated proteins and aids their processing introduced its likely role as a recognition factor for prenylated clients and tied LCA mutations to this activity.

    Evidence Yeast two-hybrid screen and cell-based farnesylation processing assay with LCA mutant panel

    PMID:14555765

    Open questions at the time
    • The specific physiological farnesylated client was not identified
    • No structural basis for prenyl recognition
  3. 2004 High

    Knockout and hypomorphic mouse models converted the in vitro prenyl-binding observation into a defined in vivo role: AIPL1 is selectively required for rod PDE6 abundance with elevated cGMP, identifying PDE6 as the critical client.

    Evidence Aipl1 knockout and graded hypomorph mice with PDE6/cGMP quantification, ERG, immunohistochemistry

    PMID:15365173 PMID:15365178

    Open questions at the time
    • Could not distinguish reduced synthesis from accelerated degradation
    • Direct physical AIPL1–PDE6 contact not yet shown
  4. 2004 Medium

    Mapping the NUB1-binding region and characterizing mutant mislocalization clarified that AIPL1 modulates NUB1 distribution and that misfolded disease alleles are themselves proteasome targets.

    Evidence Co-transfection localization assays, GST pulldown/Co-IP/Y2H with mutant panel, CD spectroscopy and ubiquitination assay

    PMID:15081406 PMID:15347646 PMID:15469903

    Open questions at the time
    • Physiological relevance of NUB1 modulation in photoreceptors unresolved
    • Whether NUB1 binding contributes to PDE6 chaperoning unclear
  5. 2006 Medium

    Single-cell physiology in hypomorphs showed AIPL1 loss perturbs the photoresponse beyond what reduced PDE6 alone predicts, hinting at broader effects on transduction components.

    Evidence Single-cell electrophysiology, ERG, Ca2+ imaging and biochemical quantification in hypomorphic mice

    PMID:16639031

    Open questions at the time
    • Additional affected transduction components not molecularly identified
    • Direct vs indirect contribution not separated
  6. 2009 High

    Pulse-chase with proteasome rescue and direct Co-IP resolved the mechanism as post-translational stabilization: AIPL1 binds PDE6α and protects nascent PDE6 from proteasomal degradation during holoenzyme assembly.

    Evidence Ex vivo retinal explant pulse-chase, proteasome inhibitor rescue, monoclonal antibody Co-IP of AIPL1–PDE6α

    PMID:19758987

    Open questions at the time
    • Structural detail of the AIPL1–PDE6α interface not defined
    • Role of cofactors in the assembly reaction unresolved
  7. 2009 High

    Rod-specific transgenic rescue demonstrated that AIPL1 acts cell-autonomously in cones, not merely through rod-derived signals, establishing a parallel requirement for cone PDE6 stability.

    Evidence Rod-specific AIPL1 transgene in Aipl1-/- mice with ERG, immunoblot of cone PDE6

    PMID:20042464

    Open questions at the time
    • Cone-specific mechanistic details deferred
    • cGMP-cyclase axis in cones not yet examined
  8. 2012 Medium

    Identifying FAT10 and UBA6 binding and the AIPL1–FAT10–NUB1 ternary complex extended AIPL1's ubiquitin-like pathway role to protection of FAT10 conjugates from NUB1-driven degradation.

    Evidence Co-IP and protein degradation assays with LCA mutant panel

    PMID:22347407

    Open questions at the time
    • Photoreceptor substrates of the FAT10 pathway unknown
    • Relationship to PDE6 chaperoning not established
  9. 2013 High

    Defining the cone-specific consequences and reconstituting chaperone activity established mechanistic divergence between rods and cones and assigned the intrinsic chaperone function to the proline-rich domain rather than PPIase catalysis.

    Evidence All-cone Aipl1-/- mouse with cGMP/RetGC1 measurement; in vitro aggregation, PPIase, and Hsp90 binding assays with PRD truncations

    PMID:23418749 PMID:24108108

    Open questions at the time
    • Mechanism linking PDE6 loss to RetGC1 reduction in cones unresolved
    • Client repertoire of the PRD-mediated chaperone activity undefined
  10. 2014 Medium

    A developmental time-course showed AIPL1 loss disrupts photoreceptor synaptic structure and downstream circuitry before degeneration, broadening the phenotypic reach of the chaperone deficit.

    Evidence Immunocytochemistry across postnatal days in Aipl1-/- retina

    PMID:24736053

    Open questions at the time
    • Whether synaptic defects are secondary to PDE6/cGMP imbalance unknown
    • Single-method time-course
  11. 2015 Medium

    Discovery of EB1/EB3 binding at the connecting cilium added a cytoskeletal/ciliary dimension and showed LCA alleles disrupt this interaction.

    Evidence Y2H, Co-IP, immunofluorescence and cryo-immunogold EM at the connecting cilium

    PMID:25799540

    Open questions at the time
    • Functional role of AIPL1 at the cilium not established
    • Relation to PDE6 trafficking unknown
  12. 2017 High

    Structural and domain-dissection work defined the molecular logic: the FKBP-like domain forms a prenyl-binding module gated by a W72 conformational switch, and both FKBP and TPR domains are needed for HSP90 binding and PDE6 catalytic stabilization, with epistasis confirmed in zebrafish.

    Evidence FKBP-domain crystal structures with isoprenyl ligands, NMR, MD, mutagenesis; in vitro PDE6 activity and HSP90 assays; zebrafish aipl1b–pde6c epistasis

    PMID:28378769 PMID:28739921 PMID:28973376

    Open questions at the time
    • Full-length AIPL1–HSP90–PDE6 architecture not yet visualized
    • How prenyl binding couples to HSP90 cycling unclear
  13. 2022 High

    Reconstitution defined the 1:2 AIPL1:HSP90 stoichiometry and TPR/helix-7 interface and, unexpectedly, showed PDE6A farnesylation is dispensable for normal rod function while AIPL1 can mature unprenylated cone PDE6C.

    Evidence Binding affinity/stoichiometry assays, TPR mutagenesis, heterologous PDE6 maturation, prenylation-deficient PDE6A mouse

    PMID:35065964

    Open questions at the time
    • Reconciliation of dispensable prenylation with the FKBP prenyl-binding module incomplete
    • In vivo necessity of each interface determinant for human disease not fully mapped
  14. 2023 High

    A cryo-EM structure of the HSP90–AIPL1 complex positioned the FKBP-like domain at the HSP90 dimer interface with the AIPL1 N-terminus in the HSP90 lumen, and showed the N-terminal residues are required for PDE6 cochaperone activity.

    Evidence 3.9 Å cryo-EM, crosslinking mass spectrometry, N-terminal deletion with PDE6 cochaperone assay

    PMID:36657440

    Open questions at the time
    • Structure of the ternary AIPL1–HSP90–PDE6 assembly not resolved
    • Dynamics of client handoff to PDE6 holoenzyme undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how AIPL1's HSP90/prenyl-recognition chaperone cycle is mechanistically coupled to its ciliary EB-protein and ubiquitin-like (NUB1/FAT10) interactions, and how these distinct activities jointly determine photoreceptor survival.
  • No integrated model linking PDE6 chaperoning, ciliary localization, and FAT10/NUB1 regulation
  • Mechanism of cone RetGC1 depletion unexplained
  • Ternary client-loaded complex not structurally defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 5 GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005929 cilium 1
Partners
EB1EB3FAT10HSP70HSP90NUB1PDE6AUBA6
Complex memberships
AIPL1–HSP90 cochaperone complex

Evidence

Reading pass · 25 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 screening, 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 processing assay Proceedings of the National Academy of Sciences of the United States of America Medium 14555765
2004 AIPL1 is essential for stability of rod cGMP phosphodiesterase (PDE6); in Aipl1-/- mouse retinas, rod PDE6 is absent and cGMP levels are elevated prior to onset of degeneration, demonstrating that AIPL1 enhances PDE6 stability. Aipl1 knockout mouse model, biochemical quantification of PDE6 and cGMP levels, immunohistochemistry, ERG Proceedings of the National Academy of Sciences of the United States of America High 15365173 15365178
2004 AIPL1 is required for biosynthesis of rod cGMP phosphodiesterase (PDE6); knockdown of AIPL1 in mice reduces PDE6 levels proportional to AIPL1 reduction while other photoreceptor proteins are unaffected, consistent with AIPL1 acting as a specialized chaperone for rod PDE biosynthesis. Aipl1 hypomorphic mouse model, quantitative immunoblotting of photoreceptor proteins, single-cell electrophysiology and ERG Proceedings of the National Academy of Sciences of the United States of America High 15365173
2002 AIPL1 interacts with the cell cycle regulator NUB1 (NEDD8 Ultimate Buster 1) as identified by yeast two-hybrid screen in retinal cDNA library and validated by co-immunoprecipitation in Y79 retinoblastoma cells. Yeast two-hybrid screen, co-immunoprecipitation in Y79 cells, immunohistochemistry Human molecular genetics Medium 12374762
2002 AIPL1 protein is localized exclusively in rod photoreceptors of the adult human retina, detected from inner segments through nuclei to synaptic spherules, but not in cone photoreceptors. Immunohistochemistry with polyclonal antibody on human retinal tissue sections, western blot on human retinal extracts Human molecular genetics Medium 11929855
2003 AIPL1 is expressed in both rod and cone photoreceptors of the developing human fetal retina, following the centroperipheral gradient of photoreceptor development, explaining why mutations cause dysfunction of both rod and cone cells in LCA. Immunohistochemistry and immunofluorescence confocal microscopy on developing human retina with characterized AIPL1 antiserum Investigative ophthalmology & visual science Medium 14638743
2004 AIPL1 modulates nuclear translocation of NUB1 by shifting its 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, and pathogenic mutations variably compromise this activity. Co-transfection in cell lines with GFP-tagged NUB1 constructs, immunofluorescence microscopy, mutagenesis of AIPL1 The Journal of biological chemistry Medium 15347646
2004 LCA-causing mutations abolish the AIPL1-NUB1 interaction; the NUB1-binding site on AIPL1 maps to residues 181–330. Some but not all LCA-associated AIPL1 mutants fail to interact with NUB1. Three independent binding assays (yeast two-hybrid, GST pulldown, co-immunoprecipitation) with panel of LCA-associated AIPL1 mutants Biochemical and biophysical research communications Medium 15081406
2004 Wild-type AIPL1 is distributed throughout nucleus and cytoplasm in transfected eukaryotic cells; disease-associated mutants W278X and A336Δ2 remain in the cytoplasm in aggresome-like ubiquitinated particles, indicating proteasomal targeting of misfolded AIPL1. Immunofluorescence microscopy in transfected cells, circular dichroism spectroscopy of recombinant protein, ubiquitination assay Biochimica et biophysica acta Medium 15469903
2008 AIPL1 interacts with molecular chaperones Hsp90 and Hsp70 via its TPR domain; LCA-causing mutations in the TPR domain compromise these interactions. AIPL1 cooperates with Hsp70, but not Hsp90, to suppress NUB1 fragment aggregation, suggesting AIPL1 functions as part of a chaperone heterocomplex. Yeast two-hybrid identification, co-immunoprecipitation validation, chaperone aggregation suppression assay, mutagenesis of TPR domain Investigative ophthalmology & visual science High 18408180
2009 AIPL1 interacts directly with the catalytic α-subunit of rod PDE6 (PDE6α); in the absence of AIPL1, newly synthesized PDE6 subunits are rapidly degraded by proteasomes, not reduced in synthesis. AIPL1 is required for proper assembly of functional rod PDE6 holoenzyme. Ex vivo pulse-label and pulse-chase analysis in retinal explants, proteasome inhibitor rescue, novel monoclonal antibody co-immunoprecipitation of AIPL1-PDE6α complex The Journal of biological chemistry High 19758987
2009 AIPL1 is directly required in cone photoreceptors for cone PDE6 stability and cone function; transgenic rod-specific rescue of AIPL1 in Aipl1-/- mice restores rod function but cone PDE6 remains markedly reduced and cones remain non-functional and degenerate. Rod-specific AIPL1 transgene rescue in Aipl1-/- mice, ERG, immunohistochemistry, immunoblotting of cone PDE6 Human molecular genetics High 20042464
2013 In all-cone photoreceptors lacking Aipl1, cone PDE6 is destabilized, fails to assemble, and loses membrane association; additionally, RetGC1 (guanylate cyclase needed for cGMP synthesis) is dramatically reduced, leading to decreased cGMP—contrasting with rods where AIPL1 loss elevates cGMP. All-cone Aipl1-/- mouse model, immunohistochemistry, immunoblotting, cGMP measurement Human molecular genetics High 24108108
2013 AIPL1 has chaperone activity that prevents aggregation of non-native proteins, enabled by its unique C-terminal proline-rich domain (PRD); the FKBP-like domain of AIPL1 is enzymatically inactive as a PPIase. The PRD acts as a negative regulator of Hsp90 binding while also being required for binding non-native client proteins. In vitro chaperone aggregation assay with recombinant proteins, PPIase activity assay, Hsp90 binding affinity measurements, PRD truncation mutants Biochemistry High 23418749
2012 AIPL1 binds non-covalently to free FAT10 and FAT10-ylated proteins and forms a ternary complex with FAT10 and NUB1. AIPL1 antagonizes NUB1-mediated proteasomal degradation of FAT10 conjugates; pathogenic AIPL1 mutations that disrupt NUB1 interaction abolish this protective effect. AIPL1 also co-immunoprecipitates UBA6, the E1 activating enzyme for FAT10. Co-immunoprecipitation, protein degradation assay with panel of LCA-associated AIPL1 mutants PloS one Medium 22347407
2017 Crystal structures of the AIPL1-FKBP domain in apo form and in complex with isoprenyl moieties reveal a unique prenyl-binding module enabled by a 'loop-out' conformation of the β4-α1 loop and a conformational 'flip-out' switch of W72. NMR identified a second major apo conformation where W72 flips into the ligand-binding pocket, rendering the protein incapable of prenyl binding; this conformation underlies pathogenicity of the V71F mutant. Crystal structure determination, NMR spectroscopy, molecular dynamics simulations, 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 directly through interaction with the farnesyl moiety. Mutations compromising the TPR domain integrity also fail to promote HSP90-dependent stabilization of PDE6α. In vitro functional assay of heterologously expressed rod PDE6, HSP90 interaction assays, mutagenesis of FKBP and TPR domains, AIPL1 splice variant characterization Human molecular genetics High 28973376
2017 Aipl1 is required for stability of cone-specific PDE6c and cone-specific guanylate cyclase zGc3 in zebrafish; the aipl1b (cone-specific) mutation genetically interacts with the pde6c mutation (eclipse), establishing epistasis between aipl1 and pde6c in the same pathway. Zebrafish aipl1b mutant (gosh), genetic epistasis with pde6c mutant (eclipse), immunoblotting, morpholino knockdown of zGc3 Scientific reports Medium 28378769
2022 The AIPL1–HSP90 complex has a stoichiometry of 1 AIPL1:2 HSP90; the TPR domain and TPR helix-7 extension are the main contributors to the AIPL1/HSP90 interface. Mutations of these determinants markedly diminish both HSP90 affinity and ability to cochaperone PDE6 maturation. Farnesylation of PDE6A is not required for its normal expression, trafficking, or signaling in rods; AIPL1 can induce maturation of unprenylated cone PDE6C. Biochemical binding assays (stoichiometry, affinity), mutagenesis of TPR determinants, heterologous expression system for PDE6 maturation, mouse model with prenylation-deficient PDE6A The Journal of biological chemistry High 35065964
2023 Cryo-EM structure at 3.9 Å of the HSP90–AIPL1 complex reveals that the FKBP-like domain of AIPL1 interacts with HSP90 at its dimer interface, and the AIPL1 N-terminus inserts into the HSP90 lumen. Multi-body refinement indicates large swing-like movements of AIPL1-FKBP. Deletion of the 7 N-terminal residues of AIPL1 decreased its ability to cochaperone PDE6. Cryo-EM structure determination, crosslinking mass spectrometry, deletion mutagenesis with PDE6 cochaperone functional assay Structure (London, England : 1993) High 36657440
2015 AIPL1 and EB proteins (EB1 and EB3) co-localize at the connecting cilia of retinal photoreceptor cells; AIPL1 interacts with EB1 and EB3 (validated by yeast two-hybrid and co-immunoprecipitation from neuroblastoma cells), and LCA-causing mutations A197P, C239R, and W278X severely compromise this interaction. Yeast two-hybrid screen of bovine retinal cDNA library, co-immunoprecipitation from SK-N-SH cells, immunofluorescence confocal microscopy, cryo-immunogold electron microscopy PloS one Medium 25799540
2020 In human iPSC-derived retinal organoids from an LCA4 patient carrying C89R AIPL1 mutation, AIPL1 and PDE6 protein levels are reduced, corroborating the chaperone-client relationship between AIPL1 and PDE6 in a human photoreceptor context. hiPSC-derived 3D retinal organoids, western blotting, immunofluorescence Scientific reports Medium 32214115
2020 The primate-specific proline-rich domain of AIPL1 is dispensable for both HSP90 interaction and PDE6 catalytic activity modulation in vitro; variants in this domain are unlikely to cause disease, with the exception of the p.A352_P355del dominant cone-rod dystrophy variant. The FKBP-like domain missense and nonsense variants in both FKBP-like and TPR domains cause loss of HSP90 interaction and PDE6 activity. In vitro HSP90 binding assay, heterologous PDE6 activity assay, minigene splicing assay, clinical correlation Scientific reports High 33067476
2006 Reduced AIPL1 delays the photoresponse, decreases its amplification constant, slows recovery, and limits the light-induced decrease in Ca²⁺ in rods. Not all phototransduction changes are attributable solely to decreased PDE or elevated cGMP/Ca²⁺, suggesting AIPL1 directly or indirectly affects multiple phototransduction components. Single-cell electrophysiology and ERG in hypomorphic Aipl1 mice, biochemical quantification of transduction proteins and enzymatic activities, fluorescent Ca²⁺ dye imaging, comparison to Y99C GCAP1 mutant rods Investigative ophthalmology & visual science Medium 16639031
2014 AIPL1 deficiency causes early reduction of postsynaptic proteins in bipolar cells and retraction of bipolar and horizontal cell dendrites prior to photoreceptor degeneration, indicating that loss of AIPL1 in photoreceptors rapidly affects synaptogenesis and retinal circuitry. Immunocytochemistry with cell-specific markers in Aipl1-/- mouse retina across postnatal days 8–150 Investigative ophthalmology & visual science Medium 24736053

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 78 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 60 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 38 27030474
2004 Retinal degeneration in Aipl1-deficient mice: a new genetic model of Leber congenital amaurosis. Brain research. Molecular brain research 38 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 30 22412862
2011 Residual electroretinograms in young Leber congenital amaurosis patients with mutations of AIPL1. Investigative ophthalmology & visual science 28 21900377
2022 Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis. Stem cell reports 27 36084639
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
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
2017 Aipl1 is required for cone photoreceptor function and survival through the stability of Pde6c and Gc3 in zebrafish. Scientific reports 20 28378769
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
2024 Effective AAV-mediated gene replacement therapy in retinal organoids modeling AIPL1-associated LCA4. Molecular therapy. Nucleic acids 18 38439910
2023 Retinal Organoids from an AIPL1 CRISPR/Cas9 Knockout Cell Line Successfully Recapitulate the Molecular Features of LCA4 Disease. International journal of molecular sciences 18 36982987
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
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
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
2025 Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study. Lancet (London, England) 12 39986747
2015 Investigation of Aberrant Splicing Induced by AIPL1 Variations as a Cause of Leber Congenital Amaurosis. Investigative ophthalmology & visual science 12 26650897
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
2022 Molecular insights into the maturation of phosphodiesterase 6 by the specialized chaperone complex of HSP90 with AIPL1. The Journal of biological chemistry 9 35065964
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
2024 Clinical and Molecular Characterization of AIPL1-Associated Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy. American journal of ophthalmology 8 38880373
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
2015 The Leber congenital amaurosis protein AIPL1 and EB proteins co-localize at the photoreceptor cilium. PloS one 6 25799540
2025 Human cone photoreceptor transplantation stimulates remodeling and restores function in AIPL1 model of end-stage Leber congenital amaurosis. Stem cell reports 5 40154478
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
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 4 24596939
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
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

Missed literature

Know a paper Affinage missed for AIPL1? Flag it for the maintainers and the community.

No submissions yet.