Affinage

IFT88

Intraflagellar transport protein 88 homolog · UniProt Q13099

Length
824 aa
Mass
93.2 kDa
Annotated
2026-06-10
74 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IFT88 is an essential, evolutionarily conserved subunit of intraflagellar transport (IFT) complex B that drives assembly and maintenance of cilia and flagella across eukaryotes, from Chlamydomonas and C. elegans to mammalian kidney and photoreceptors (PMID:11062270, PMID:11290289, PMID:11916979). Within IFT-B it is a TPR-motif protein that directly binds IFT52 and IFT46 to form a core ternary scaffold, which in turn docks IFT70 via the IFT52–IFT88 dimer—an interaction required for ciliogenesis (PMID:20435895, PMID:29654116). IFT88 undergoes bidirectional IFT particle movement within the axoneme (PMID:11290289), and its ciliary compartmentalization is gated by the transition zone (PMID:29866362). Cargo delivery toward the cilium depends on DGKδ-triggered release of IFT88-containing COPII vesicles from ER exit sites, supporting Hedgehog signaling (PMID:28706295), and IFT88 recruitment to the basal body lies downstream of CPAP/WDR62 (PMID:31816041). Through ciliary Hedgehog signaling, IFT88 governs developmental programs including chondrocyte growth-plate signaling and Wnt/β-catenin balance (PMID:23034798) and cranial neural crest proliferation during palatogenesis, where its loss causes cleft lip and palate (PMID:28069795). Transgenic re-expression of Tg737/IFT88 rescues collecting-duct cystic kidney disease in mutant mice, establishing it as the causative gene (PMID:8887283). Beyond cilia, IFT88 has multiple non-ciliary roles: it localizes to centrosomes via its TPR motifs and interacts with the Rb-binding protein Che-1 to restrain the G1–S transition (PMID:17264151); it participates in a dynein1-driven complex that delivers microtubule-nucleating factors to spindle poles for astral microtubule formation and spindle orientation (PMID:21441926); it concentrates at k-fiber minus-ends to recruit NuMA for k-fiber re-anchoring (PMID:31312011); and it organizes leading-edge microtubules for cell migration and oriented cell division during gastrulation independently of cilia (PMID:24095732, PMID:26465598). In spermatids, MEIG1 recruits IFT88 (with IFT20) to the manchette to support intramanchette transport for flagellum biogenesis (PMID:21337470, PMID:35257720). IFT88 abundance is controlled by competing post-translational modifications: UFL1-mediated UFMylation at K572 antagonizes PJA2-driven ubiquitination and proteasomal degradation (PMID:41272290), while XIAP ubiquitinates IFT88 in response to TGF-β to promote its degradation during fibrogenesis (PMID:38351372).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 2000 High

    Established the foundational role of IFT88 as an essential IFT particle subunit required for ciliary and flagellar assembly, answering whether this protein is causally needed to build cilia.

    Evidence Insertional mutagenesis in Chlamydomonas and Tg737 mutant mouse analysis with EM

    PMID:11062270

    Open questions at the time
    • Did not resolve where IFT88 sits within the IFT particle architecture
    • Mechanism of transport not directly visualized
  2. 2001 High

    Demonstrated that the IFT88 ortholog physically moves as part of IFT particles along the axoneme, linking the gene's loss-of-function phenotype to active transport behavior.

    Evidence GFP-fusion rescue and time-lapse live imaging in C. elegans osm-5 mutants

    PMID:11290289

    Open questions at the time
    • Motor and cargo specificity not defined
    • Direct binding partners within IFT-B not identified
  3. 2002 High

    Extended IFT88's ciliary requirement to specialized sensory cilia by showing it is needed for photoreceptor outer segment assembly and maintenance.

    Evidence Immunolocalization in connecting cilia plus Tg737 mutant retinal phenotyping

    PMID:11916979

    Open questions at the time
    • Specific cargoes transported in photoreceptors not identified
  4. 1996 High

    Provided definitive causal proof that Tg737/IFT88 is the gene responsible for cystic kidney disease by rescuing the phenotype with wild-type cDNA.

    Evidence Transgenic rescue with renal function and EGFr localization readouts

    PMID:8887283

    Open questions at the time
    • Molecular mechanism linking ciliary defect to cystogenesis not established
  5. 2010 High

    Defined the molecular architecture by which IFT88 integrates into IFT-B, showing it directly binds IFT52 and IFT46 to form a core ternary scaffold.

    Evidence Yeast two-hybrid, bacterial co-expression pulldown, chemical cross-linking, and in vivo rescue

    PMID:20435895

    Open questions at the time
    • Full IFT-B stoichiometry and structure not resolved
    • How the scaffold couples to motors unaddressed
  6. 2007 High

    Revealed an unexpected cilia-independent role at the centrosome and in cell-cycle control, showing IFT88 restrains G1–S transition via Che-1.

    Evidence Centrosomal fractionation, RNAi/overexpression with cell-cycle FACS, Co-IP, and TPR-deletion mutagenesis

    PMID:17264151

    Open questions at the time
    • Mechanism by which Che-1 binding modulates Rb not detailed
    • Single-lab observation of cell-cycle phenotype
  7. 2011 High

    Identified a mitotic function in which IFT88 acts within a dynein1-driven complex delivering microtubule-nucleating factors to spindle poles for spindle orientation.

    Evidence RNAi across human cells, mouse Tg737(orpk) cells, and zebrafish embryos with live imaging and Co-IP

    PMID:21441926

    Open questions at the time
    • Direct nucleating cargo identity not fully defined
    • How IFT88 selects mitotic vs ciliary roles unknown
  8. 2011 Medium

    Showed IFT88 functions in spermatid manchette-associated vesicle and organelle transport during flagellum biogenesis, broadening its trafficking role.

    Evidence Immunocytochemistry in wild-type/Ift88 mutant spermatids with BFA and nocodazole disruption

    PMID:21337470

    Open questions at the time
    • Upstream targeting machinery to the manchette not yet identified at this stage
    • Direct cargo-binding mechanism not shown
  9. 2012 Medium

    Connected ciliary IFT88 to developmental signaling crosstalk, showing its loss disrupts Hedgehog and de-represses Wnt/β-catenin in growth-plate chondrocytes.

    Evidence Conditional Ift88 KO in chondrocytes with expression profiling, in situ hybridization, and Shh treatment

    PMID:23034798

    Open questions at the time
    • Direct molecular step linking IFT88 to Sfrp5 not defined
    • Single-lab pathway analysis
  10. 2013 High

    Used complete maternal+zygotic loss to dissociate cilia from IFT88's role in oriented cell division, establishing a genuinely cilia-independent developmental function.

    Evidence Maternal+zygotic ift88 zebrafish mutants with PCP marker and division-orientation analysis

    PMID:24095732

    Open questions at the time
    • Molecular effector for oriented division not identified
    • Relationship to spindle-pole role not connected
  11. 2015 Medium

    Defined a cilia-independent cytoskeletal role in cell migration, showing IFT88 organizes leading-edge microtubules without altering MT dynamics or nucleation.

    Evidence siRNA in MDCK cells with wound-healing assays and confocal MT imaging

    PMID:26465598

    Open questions at the time
    • Direct MT-organizing partners not identified
    • Single primary method for MT analysis
  12. 2017 Medium

    Resolved a step in ciliary cargo delivery, showing DGKδ triggers release of IFT88-containing COPII vesicles from ER exit sites to feed Hedgehog signaling.

    Evidence Co-IP of IFT88 with DGKδ, COPII co-localization, and Shh reporter assays with RNAi

    PMID:28706295

    Open questions at the time
    • Direct vs indirect IFT88–DGKδ interaction not fully resolved
    • Vesicle docking machinery downstream not defined
  13. 2017 Medium

    Demonstrated a tissue-level developmental requirement, showing neural-crest IFT88 loss eliminates cilia, lowers Shh, and causes cleft lip and palate.

    Evidence Tissue-specific conditional KO mice (Wnt1-Cre, Osr2KI-Cre) with cilia, Shh, and proliferation readouts

    PMID:28069795

    Open questions at the time
    • Direct molecular target of Shh dysregulation not pinpointed
    • Single-lab study
  14. 2018 Medium

    Placed IFT88 downstream of the transition zone, showing transition-zone integrity gates IFT88 compartmentalization within the cilium.

    Evidence CRISPR TCTN2 KO with super-resolution imaging and RPGRIP1L/cytochalasin D perturbations

    PMID:29866362

    Open questions at the time
    • Molecular determinant of IFT88 gating not identified
    • Functional consequence of lumen leakage not measured
  15. 2018 Medium

    Showed a Hedgehog-independent role in receptor-mediated endocytosis, where IFT88 maintains LRP-1 ciliary-base distribution and protease clearance.

    Evidence IFT88(orpk) hypomorphic chondrocytes with aggrecanase, LRP-1 imaging, and clearance assays

    PMID:29920219

    Open questions at the time
    • Mechanism connecting IFT88 to LRP-1 trafficking not defined
    • Single-cell-type evidence
  16. 2018 High

    Mapped the IFT-B docking hierarchy further by showing IFT70 binds the IFT52–IFT88 dimer in a manner required for ciliogenesis.

    Evidence IFT70 double-KO cells, deletion mutagenesis, and Co-IP interaction mapping with functional rescue

    PMID:29654116

    Open questions at the time
    • Higher-order IFT-B assembly order not fully ordered
    • Structural detail of the interface not resolved
  17. 2019 Medium

    Refined IFT88's mitotic function, showing it concentrates at k-fiber minus-ends and recruits NuMA for k-fiber re-anchoring and chromosome alignment.

    Evidence Laser ablation with IFT88 localization, Co-IP with NuMA, and nocodazole washout under depletion

    PMID:31312011

    Open questions at the time
    • Direct vs scaffolded IFT88–NuMA binding not separated
    • Relationship to the spindle-pole dynein complex not integrated
  18. 2020 Medium

    Placed IFT88 downstream of CPAP/WDR62 in the ciliogenesis pathway, showing WDR62-mutant failure to recruit CPAP impairs IFT88 basal-body recruitment.

    Evidence CRISPR WDR62-mutant mice with CPAP/IFT88 basal-body imaging and radial glia differentiation assays

    PMID:31816041

    Open questions at the time
    • Direct molecular link between CPAP and IFT88 recruitment not defined
  19. 2021 Medium

    Identified a cilium-independent role in periciliary membrane compartment organization that distinguishes IFT88 from kinesin-2.

    Evidence Comparative Ift88/Kif3a knockdown in MDCK cells and osm-5/osm-3 C. elegans mutants with exclusion assay

    PMID:34753064

    Open questions at the time
    • Molecular mechanism of PCMC organization unknown
    • Direct membrane partners not identified
  20. 2021 Medium

    Linked IFT88 to autophagy regulation in the kidney, showing its loss suppresses cisplatin-induced autophagy and worsens acute kidney injury.

    Evidence Proximal-tubule-specific KO mice and HK-2 knockdown with autophagy flux assays and rescue

    PMID:34251272

    Open questions at the time
    • Direct molecular step linking IFT88 to autophagy machinery unknown
    • Cilia-dependence not separated
  21. 2021 Medium

    Connected fibroblast IFT88 to ECM regulation and downstream cardiac electrophysiology, broadening its physiological footprint.

    Evidence siRNA in neonatal rat fibroblasts with CM-FB co-culture, electrical mapping, and ECM gene analysis

    PMID:36467697

    Open questions at the time
    • Signaling pathway linking IFT88 to ECM genes not defined
    • Single co-culture model
  22. 2022 Medium

    Identified the upstream recruiter for spermatid IFT88, showing MEIG1 directs IFT88/IFT20 to the manchette as a complex.

    Evidence Co-IP from testis, Meig1 and conditional Ift20 KO localization, and sucrose gradient sedimentation

    PMID:35257720

    Open questions at the time
    • Direct vs indirect MEIG1–IFT88 interaction not resolved
    • How the complex engages microtubule motors unaddressed
  23. 2024 Medium

    Established degradative control of IFT88, showing XIAP ubiquitinates it under TGF-β to promote fibrogenesis.

    Evidence XIAP E3 identification, ubiquitination assays, and Ift88 KO + CCl4 liver fibrosis model with rescue

    PMID:38351372

    Open questions at the time
    • Ubiquitination site not mapped in this study
    • Cilia-dependence of the fibrosis effect not separated
  24. 2025 High

    Defined a stabilizing post-translational switch, showing UFL1-mediated UFMylation at K572 antagonizes PJA2 ubiquitination to protect IFT88 and sustain ciliogenesis.

    Evidence UFMylation site mapping, K572R mutagenesis, ubiquitination assays, competing-ligase identification, and UFL1 KO mouse phenotyping

    PMID:41272290

    Open questions at the time
    • Signals controlling UFL1 vs PJA2 balance not defined
    • Structural effect of K572 modification unknown
  25. 2025 Medium

    Linked ciliary IFT88 to brown-fat thermogenesis via ketogenesis, showing its loss impairs HMGCS2-dependent β-hydroxybutyrate production.

    Evidence BAT-specific Ift88 KO mice with metabolic assays and β-HB/thermoneutral rescue (preprint)

    PMID:bio_10.1101_2025.11.12.687971

    Open questions at the time
    • Signaling link from cilia to HMGCS2 not defined
    • Preprint, single lab
  26. 2025 Low

    Implicated IFT88 in early ciliogenesis membrane remodeling, showing it is required for tubular membrane intermediate formation at the mother centriole.

    Evidence 3D volume EM of IFT88-depleted cells with quantitative intermediate analysis (preprint)

    PMID:bio_10.1101_2025.08.20.670930

    Open questions at the time
    • Single structural imaging approach with no biochemical follow-up
    • Direct role vs indirect consequence of IFT loss not separated
  27. 2025 Medium

    Identified an ion-channel regulatory role, showing IFT88 suppresses TRPV4-mediated calcium influx and autoregulates C/EBPα in endplate chondrocytes.

    Evidence Docking, Co-IP, dual-luciferase, flow cytometry, and rat tail crush model with IFT88 overexpression

    PMID:40441296

    Open questions at the time
    • Direct IFT88–TRPV4 interaction mechanism not resolved
    • Cilia-dependence not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How IFT88 partitions among its ciliary, centrosomal, mitotic, migratory, and trafficking roles—and what molecular signals or modifications select between them—remains unresolved.
  • No unifying mechanism distinguishing ciliary vs non-ciliary pools
  • Structural basis of IFT-B incorporation vs centrosomal/spindle binding not defined
  • Regulation of PTM-driven stability across tissues not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0060090 molecular adaptor activity 4
Localization
GO:0005929 cilium 4 GO:0005815 microtubule organizing center 3 GO:0005856 cytoskeleton 3 GO:0031410 cytoplasmic vesicle 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CHE-1/AATFDGKDIFT20IFT46IFT52IFT70MEIG1NUMA
Complex memberships
IFT complex B

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 IFT88 (Chlamydomonas) / Tg737 (mouse) is required for assembly of cilia and flagella; Chlamydomonas insertional mutants lacking IFT88 have no flagella, and Tg737 mutant mice have shorter primary cilia in the kidney, demonstrating IFT88 is an essential IFT particle subunit for ciliary assembly in both unicellular and mammalian contexts. Insertional mutagenesis in Chlamydomonas; mouse mutant analysis with electron microscopy; cDNA cloning and sequence comparison The Journal of cell biology High 11062270
2001 C. elegans OSM-5 (IFT88 ortholog) localizes to the cilium base and axoneme and undergoes intraflagellar transport particle movement within cilia, as shown by OSM-5::GFP time-lapse imaging; osm-5 mutants have ciliary defects consistent with a ciliogenic role. Transgenic GFP fusion rescue of osm-5 mutants; time-lapse live imaging; immunofluorescence; DAF-19 transcription factor regulation confirmed by expression analysis Development (Cambridge, England) High 11290289
2002 IFT88/Tg737 protein localizes to photoreceptor connecting cilia, and loss-of-function mutation in Tg737/IFT88 causes abnormal outer segment development and retinal degeneration, demonstrating that IFT is required for photoreceptor outer segment assembly and maintenance. Immunolocalization of IFT particle proteins in photoreceptors; analysis of Tg737 mutant mouse retinal phenotype by electron microscopy and histology The Journal of cell biology High 11916979
1996 Transgenic re-expression of wild-type Tg737 cDNA in Tg737 mutant mice restores normal renal function and normal basolateral EGFr localization in collecting duct epithelium, directly confirming Tg737 as the causative gene for collecting duct cyst formation. Transgenic rescue experiment; renal function tests; immunohistochemistry for EGFr localization Kidney international High 8887283
2007 IFT88/polaris localizes to the centrosome throughout the cell cycle in a microtubule- and dynein-independent manner, mediated by its TPR motifs. Overexpression prevents G1-S transition and induces apoptosis; RNAi depletion promotes cell-cycle progression to S, G2, and M phases. IFT88 interacts with Che-1, an Rb-binding protein that inhibits Rb growth-suppressing function. Immunofluorescence/fractionation for centrosomal localization; RNAi knockdown and overexpression with cell-cycle FACS analysis; Co-IP for IFT88–Che-1 interaction; TPR domain deletion mutagenesis Journal of cell science High 17264151
2011 In mitosis, IFT88 localizes to spindle poles and is part of a dynein1-driven complex that transports peripheral microtubule clusters containing microtubule-nucleating proteins to spindle poles to ensure proper astral microtubule array formation and spindle orientation. IFT88 depletion causes mitotic defects in human cells, Tg737(orpk) kidney cells, and zebrafish embryos. RNAi depletion in human cells; analysis of Tg737(orpk) mouse mutant kidney cells; zebrafish embryo knockdown; live-cell imaging of spindle dynamics; Co-IP for dynein1 complex Nature cell biology High 21441926
2010 IFT88 directly interacts with IFT52 and IFT46 within IFT complex B, and these three proteins can form a ternary complex. The IFT52–IFT88 interaction was confirmed by chemical cross-linking. Yeast two-hybrid; bacterial coexpression pulldown; chemical cross-linking; in vivo electroporation rescue of ift46 mutant The Journal of biological chemistry High 20435895
2018 IFT70 interacts with the IFT52–IFT88 dimer within IFT-B; deletion of the first TPR repeat or the terminal α36 helix of IFT70 abolishes its interaction with the IFT52–IFT88 dimer and abrogates ciliogenesis rescue in IFT70 knockout cells. IFT70A/B double knockout cells; exogenous expression rescue; deletion mutagenesis of IFT70; Co-IP/pulldown to map IFT70–IFT52–IFT88 interaction Biology open High 29654116
2013 In maternal+zygotic ift88 mutant zebrafish embryos (which never form cilia), planar cell polarity (PCP) is established normally, demonstrating cilia are not required for PCP. However, IFT88 plays a cilia-independent role in controlling oriented cell divisions during gastrulation and neurulation. Generation of maternal+zygotic IFT88 zebrafish mutants; PCP marker analysis; division orientation measurements Cell reports High 24095732
2015 Loss of Ift88 impairs cell migration independently of cilia; Ift88-depleted MDCK cells show defective leading-edge polarization and fewer microtubules at the leading edge, without affecting MT dynamics or nucleation. siRNA knockdown in MDCK cells; wound-healing/migration assays; confocal microscopy of MT organization; cilia-deficient controls PloS one Medium 26465598
2017 DGKδ (an ER-resident lipid kinase) interacts with IFT88 and triggers release of IFT88-containing COPII-coated vesicles from ER exit sites (ERES), facilitating delivery of ciliary cargo toward the primary cilium. RNAi of DGKδ impairs IFT88 vesicle release and Hedgehog signaling. Co-IP of IFT88 with DGKδ; association with COPII vesicles by co-localization; RNAi and knockout strategies; Shh signaling reporter assays in vitro and in vivo Scientific reports Medium 28706295
2019 IFT88 concentrates at kinetochore fiber (k-fiber) minus-ends, interacts with NuMA, and is required for NuMA enrichment at newly generated k-fiber minus-ends to facilitate k-fiber re-anchoring into the spindle and proper chromosome alignment. MT laser ablation followed by IFT88 localization; Co-IP of IFT88 with NuMA; nocodazole washout with IFT88 depletion; chromosome alignment assay Scientific reports Medium 31312011
2011 IFT88 localizes to the trans-Golgi network of spermatids and is present in proacrosomal vesicles, along acrosome membranes, and the head-tail coupling apparatus. Loss of IFT88 causes abnormal spermatid head shaping, tail absence, and blockade of GMAP210-stained vesicle and mitochondrial progression through the manchette. Immunocytochemistry in wild-type and Ift88 mutant spermatids; Brefeldin-A and nocodazole disruption of Golgi/microtubules Developmental dynamics Medium 21337470
2022 MEIG1 is required for manchette localization of IFT88 (and IFT20) in elongating spermatids; Co-IP from mouse testis confirms MEIG1, IFT20, and IFT88 form a complex; in Meig1 KO mice, IFT88 and IFT20 are absent from the manchette and drift to lighter sucrose gradient fractions, while MEIG1 localization is unchanged in conditional Ift20 KO mice, placing MEIG1 upstream of IFT88 manchette targeting. Co-IP from mouse testis; Meig1 KO mouse analysis by immunofluorescence; sucrose gradient sedimentation; conditional Ift20 KO Developmental biology Medium 35257720
2024 XIAP functions as an E3 ubiquitin ligase for IFT88; TGF-β enhances XIAP-mediated ubiquitination of IFT88, promoting its proteasomal degradation. Blocking XIAP-mediated IFT88 degradation ablates TGF-β-induced HSC activation and liver fibrosis. Ift88-KO mice are more susceptible to carbon tetrachloride-induced liver fibrosis. Mechanistic studies identifying XIAP as E3 ligase; ubiquitination assays; Ift88 KO mouse + CCl4 fibrosis model; rescue experiments blocking XIAP EMBO reports Medium 38351372
2025 UFL1 UFMylates IFT88 at lysine 572; this UFMylation antagonizes ubiquitination of IFT88 by PJA2 E3 ligase, preventing proteasomal degradation. A K572R mutant of IFT88 shows increased ubiquitination and reduced stability; UFL1 genetic ablation in mice causes severe ciliary defects in multiple tissues. UFMylation site mapping (K572); site-directed mutagenesis (K572R); ubiquitination assays; UFL1 KO mouse phenotyping; identification of PJA2 as the competing E3 ligase Cell death and differentiation High 41272290
2018 Disruption of IFT88 (hypomorphic mutation) redistributes LRP-1 receptor away from the ciliary base hot spot, increases LRP-1 shedding, and reduces the rate of extracellular protease (aggrecanase) clearance from chondrocytes, demonstrating an IFT88-dependent, Hedgehog-independent role in LRP-1-mediated endocytosis. IFT88(orpk) hypomorphic chondrocyte cell line; aggrecanase activity assay; confocal imaging of LRP-1 distribution; protease clearance assay FASEB journal Medium 29920219
2018 TCTN2 depletion causes leakage of IFT88 from the ciliary axoneme toward the basal body lumen; super-resolution microscopy shows IFT88 lumen occupancy also occurs in RPGRIP1L-depleted and cytochalasin D-treated cells, indicating the transition zone gates IFT88 compartmentalization. CRISPR/Cas9 TCTN2 KO; super-resolution (STORM/SIM) and widefield microscopy; quantitative localization analysis; siRPGRIP1L and cytochalasin D perturbations Biophysical journal Medium 29866362
2012 Deletion of Ift88 in chondrocytes disrupts Hedgehog (Ihh) signaling, downregulates Sfrp5 (an extracellular Wnt antagonist that is a downstream Hh target), and leads to increased nuclear β-catenin and Wnt/β-catenin signaling specifically in growth plate columnar cells. Conditional Ift88 KO in chondrocytes; gene expression profiling; pathway analysis; in situ hybridization for Axin2, Lef1; immunohistochemistry for nuclear β-catenin; Shh treatment of rib chondrocytes Journal of orthopaedic research Medium 23034798
2017 Loss of Ift88 in cranial neural crest cells (Wnt1-Cre;Ift88fl/fl mice) eliminates primary cilia from palatal mesenchyme, decreases neural crest cell proliferation, and downregulates Shh signaling in the palatal mesenchyme, leading to bilateral cleft lip and palate. Palatal mesenchyme-specific loss (Osr2KI-Cre;Ift88fl/fl) produces isolated cleft palate. Conditional KO mice (Wnt1-Cre and Osr2KI-Cre); immunofluorescence for cilia; Shh pathway analysis; cell proliferation assays Human molecular genetics Medium 28069795
2021 IFT88 deficiency in proximal tubular cells suppresses cisplatin-induced autophagy; autophagy activator Tat-beclin 1 partially rescues IFT88-associated cell death; re-expression of IFT88 partially restores autophagy in knockdown cells. Proximal tubule-specific IFT88 KO mice exhibit more severe AKI than wild-type upon cisplatin treatment. Proximal tubule-specific IFT88 KO mice; siRNA knockdown in HK-2 cells; autophagy flux assays; pharmacological autophagy activator rescue; IFT88 re-expression American journal of physiology. Renal physiology Medium 34251272
2021 IFT88 knockdown in fibroblasts causes significant upregulation of ECM genes (Fn1, Col1a1, Ctgf), reduces conduction velocity in cardiomyocyte monolayers, and increases conduction block, demonstrating that ciliary IFT88 in fibroblasts regulates ECM deposition and thereby cardiac electrophysiology. siRNA knockdown of Ift88 in neonatal rat fibroblasts; CM-FB co-culture; electrical mapping; gene expression analysis Frontiers in physiology Medium 36467697
2020 WDR62 mutant proteins (V66M, R439H) localize to the basal body but fail to recruit CPAP; as a consequence, IFT88 recruitment is deficient, leading to impaired ciliogenesis and premature radial glia differentiation, placing CPAP upstream of IFT88 in the ciliogenesis pathway. CRISPR/Cas9 WDR62 mutant mice; immunofluorescence for CPAP and IFT88 at basal body; ciliogenesis and radial glia differentiation assays Human molecular genetics Medium 31816041
2021 Ift88, but not Kif3a (Kinesin-2 subunit), is required for establishment of the periciliary membrane compartment (PCMC) in MDCK cells and in C. elegans (osm-5 mutants lack PCMC while osm-3/kinesin-2 mutants form PCMC normally), revealing an IFT-B1-independent, cilium-independent function of IFT88 in PCMC organization. Ift88 KD in MDCK cells; C. elegans osm-5 and osm-3 mutant analysis; Kif3a KD comparison; fluorescent exclusion assay for PCMC; split IFT-B1 mutants Biochemical and biophysical research communications Medium 34753064
1995 The human hTg737 gene encodes a protein containing tetratricopeptide repeat (TPR) motifs, is 95% identical to the mouse Tg737 protein, and maps to chromosome 13q12.1. It is broadly expressed including in kidney and liver. cDNA cloning and sequencing; chromosome mapping (FISH/hybrid panels); Northern blot expression analysis Human molecular genetics Medium 7633404
2025 Loss of primary cilia specifically in brown adipose tissue (BAT; Ucp1-Cre;Ift88 fl/fl) causes neonatal lethality from thermogenesis failure despite preserved UCP1 expression; the mechanism involves IFT88-dependent suppression of HMGCS2 downregulation and ROS production, impairing ketogenesis required for non-shivering thermogenesis. Neonatal lethality is rescued by thermoneutral housing or β-hydroxybutyrate supplementation. BAT-specific Ift88 conditional KO mice; metabolic assays (ketone body levels, ROS); qPCR for Hmgcs2; rescue by thermoneutral housing and β-HB supplementation bioRxivpreprint Medium bio_10.1101_2025.11.12.687971
2025 IFT88 is required for formation of tubular membrane intermediates (C-shaped and toroidal) during early ciliogenesis at the mother centriole; absence of IFT88 blocks progression through these membrane trafficking steps upstream of axoneme growth. 3D volume EM (isotropic ultrastructure imaging) of IFT88-depleted cells; quantitative analysis of ciliogenesis membrane intermediates bioRxivpreprint Low bio_10.1101_2025.08.20.670930
2025 IFT88 inhibits TRPV4-mediated calcium influx in endplate chondrocytes; mechanistic studies show IFT88 negatively regulates its own transcription factor C/EBPα under abnormal stress and reduces TRPV4 hyperactivation, thereby lowering intracellular calcium, oxidative stress, and Wnt pathway activation. In vivo IFT88 overexpression maintains disc height and reduces endplate ossification. Molecular docking; co-immunoprecipitation; dual-luciferase assays; flow cytometry (calcium/ROS); rat tail crush model; IFT88 overexpression in vivo Journal of advanced research Medium 40441296

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. The Journal of cell biology 916 11062270
2002 The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. The Journal of cell biology 407 11916979
2001 The C. elegans homolog of the murine cystic kidney disease gene Tg737 functions in a ciliogenic pathway and is disrupted in osm-5 mutant worms. Development (Cambridge, England) 196 11290289
2007 The intraflagellar transport component IFT88/polaris is a centrosomal protein regulating G1-S transition in non-ciliated cells. Journal of cell science 151 17264151
2011 The cilia protein IFT88 is required for spindle orientation in mitosis. Nature cell biology 147 21441926
2003 Loss of the Tg737 protein results in skeletal patterning defects. Developmental dynamics : an official publication of the American Association of Anatomists 115 12701101
2011 GMAP210 and IFT88 are present in the spermatid golgi apparatus and participate in the development of the acrosome-acroplaxome complex, head-tail coupling apparatus and tail. Developmental dynamics : an official publication of the American Association of Anatomists 85 21337470
2005 Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737(orpk) mutant mice. Laboratory investigation; a journal of technical methods and pathology 81 15580285
2009 Early defects in photoreceptor outer segment morphogenesis in zebrafish ift57, ift88 and ift172 Intraflagellar Transport mutants. Vision research 80 19136023
2010 Direct interactions of intraflagellar transport complex B proteins IFT88, IFT52, and IFT46. The Journal of biological chemistry 68 20435895
2009 Zebrafish ift57, ift88, and ift172 intraflagellar transport mutants disrupt cilia but do not affect hedgehog signaling. Developmental dynamics : an official publication of the American Association of Anatomists 60 19517571
2017 Intraflagellar transport 88 (IFT88) is crucial for craniofacial development in mice and is a candidate gene for human cleft lip and palate. Human molecular genetics 53 28069795
2015 A Cilia Independent Role of Ift88/Polaris during Cell Migration. PloS one 46 26465598
2012 Ift88 regulates Hedgehog signaling, Sfrp5 expression, and β-catenin activity in post-natal growth plate. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 45 23034798
2013 IFT88 plays a cilia- and PCP-independent role in controlling oriented cell divisions during vertebrate embryonic development. Cell reports 41 24095732
2006 Altered pH(i) regulation and Na(+)/HCO3(-) transporter activity in choroid plexus of cilia-defective Tg737(orpk) mutant mouse. American journal of physiology. Cell physiology 41 17182727
2003 Delayed cystogenesis and increased ciliogenesis associated with the re-expression of polaris in Tg737 mutant mice. Kidney international 41 12631338
2018 Robust interaction of IFT70 with IFT52-IFT88 in the IFT-B complex is required for ciliogenesis. Biology open 40 29654116
1995 Characterization of the human homologue of the mouse Tg737 candidate polycystic kidney disease gene. Human molecular genetics 38 7633404
2020 The association of microcephaly protein WDR62 with CPAP/IFT88 is required for cilia formation and neocortical development. Human molecular genetics 35 31816041
1996 Functional correction of renal defects in a mouse model for ARPKD through expression of the cloned wild-type Tg737 cDNA. Kidney international 35 8887283
2020 Endothelial-specific Loss of IFT88 Promotes Endothelial-to-Mesenchymal Transition and Exacerbates Bleomycin-induced Pulmonary Fibrosis. Scientific reports 34 32161282
2018 Loss-of-function of IFT88 determines metabolic phenotypes in thyroid cancer. Oncogene 30 29743590
2015 IFT88 influences chondrocyte actin organization and biomechanics. Osteoarthritis and cartilage 29 26493329
1997 The tetratricopeptide repeat containing Tg737 gene is a liver neoplasia tumor suppressor gene. Oncogene 29 9362446
2015 TGF-β Suppresses Ift88 Expression in Chondrocytic ATDC5 Cells. Journal of cellular physiology 24 25828538
2021 Decreased IFT88 expression with primary cilia shortening causes mitochondrial dysfunction in cisplatin-induced tubular injury. American journal of physiology. Renal physiology 23 34338030
2024 XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis. EMBO reports 21 38351372
2021 IFT88 deficiency in proximal tubular cells exaggerates cisplatin-induced injury by suppressing autophagy. American journal of physiology. Renal physiology 18 34251272
2017 Tg737 regulates epithelial-mesenchymal transition and cancer stem cell properties via a negative feedback circuit between Snail and HNF4α during liver stem cell malignant transformation. Cancer letters 18 28536011
2018 Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT88 Lumen Leakage and Ciliary Weakening. Biophysical journal 17 29866362
2018 IFT88 mutations identified in individuals with non-syndromic recessive retinal degeneration result in abnormal ciliogenesis. Human genetics 17 29978320
2016 MicroRNA-548a-5p promotes proliferation and inhibits apoptosis in hepatocellular carcinoma cells by targeting Tg737. World journal of gastroenterology 17 27340352
2018 Cilia protein IFT88 regulates extracellular protease activity by optimizing LRP-1-mediated endocytosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 29920219
2017 DGKδ triggers endoplasmic reticulum release of IFT88-containing vesicles destined for the assembly of primary cilia. Scientific reports 16 28706295
2019 Ift88 is involved in mandibular development. Journal of anatomy 15 31657471
2012 Tg737 signaling is required for hypoxia-enhanced invasion and migration of hepatoma cells. Journal of experimental & clinical cancer research : CR 15 22974282
2022 Ciliary IFT88 Protects Coordinated Adolescent Growth Plate Ossification From Disruptive Physiological Mechanical Forces. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 14 35038201
2022 Piezo1 and IFT88 synergistically regulate mandibular condylar chondrocyte differentiation under cyclic tensile strain. Tissue & cell 13 35279604
1995 Sequence analysis of the human hTg737 gene and its polymorphic sites in patients with autosomal recessive polycystic kidney disease. Mammalian genome : official journal of the International Mammalian Genome Society 13 8597639
2017 Transcriptome profiling identifies a recurrent CRYL1-IFT88 chimeric transcript in hepatocellular carcinoma. Oncotarget 12 28489570
2011 Tg737 inhibition results in malignant transformation in fetal liver stem/progenitor cells by promoting cell-cycle progression and differentiation arrest. Molecular carcinogenesis 12 21837759
2022 MEIG1 determines the manchette localization of IFT20 and IFT88, two intraflagellar transport components in male germ cells. Developmental biology 11 35257720
1999 Structure and expression of Tg737, a putative tumor suppressor gene, in human hepatocellular carcinomas. Hepatology (Baltimore, Md.) 11 10462374
2022 Knockdown of Ift88 in fibroblasts causes extracellular matrix remodeling and decreases conduction velocity in cardiomyocyte monolayers. Frontiers in physiology 9 36467697
2019 Ift88 limits bone formation in maxillary process through suppressing apoptosis. Archives of oral biology 9 30878609
2019 IFT88 controls NuMA enrichment at k-fibers minus-ends to facilitate their re-anchoring into mitotic spindles. Scientific reports 9 31312011
2022 Ift88 regulates enamel formation via involving Shh signaling. Oral diseases 8 35189017
2021 Sex-Dependent Effects of Nephron Ift88 Disruption on BP, Renal Function, and Cystogenesis. Journal of the American Society of Nephrology : JASN 8 34045314
2018 Role of IFT88 in icariin‑regulated maintenance of the chondrocyte phenotype. Molecular medicine reports 8 29393439
2014 Normal mammary development and function in mice with Ift88 deleted in MMTV- and K14-Cre expressing cells. Cilia 7 24594320
2025 Ciliary and Non-Ciliary Roles of IFT88 in Development and Diseases. International journal of molecular sciences 6 40076734
2022 Profiling renal sodium transporters in mice with nephron Ift88 disruption: Association with sex, cysts, and blood pressure. Physiological reports 5 35274831
2022 Depletion of Ift88 in thymic epithelial cells affects thymic synapse and T-cell differentiation in aged mice. Anatomical science international 5 35435578
2021 Multiomic identification of factors associated with progression to cystic kidney disease in mice with nephron Ift88 disruption. American journal of physiology. Renal physiology 5 34927449
2025 Temporal ablation of the ciliary protein IFT88 alters normal brainwave patterns. Scientific reports 4 39747370
2023 Cilia-associated wound repair mediated by IFT88 in retinal pigment epithelium. Scientific reports 4 37211572
2019 Association of IFT88 gene variants with nonsyndromic cleft lip with or without cleft palate. Birth defects research 4 30953423
2017 Basic fibroblast growth factor increases IFT88 expression in chondrocytes. Molecular medicine reports 4 28901443
2022 Multifaceted investigation underlies diverse mechanisms contributing to the downregulation of Hedgehog pathway-associated genes INTU and IFT88 in lung adenocarcinoma and uterine corpus endometrial carcinoma. Aging 3 36084949
2025 Ciliary IFT88 inhibits intervertebral disc degeneration under excessive mechanical stress by regulating endplate cartilage calcification. Journal of advanced research 2 40441296
2025 Macrophage Accumulation and Cyst Expansion in Pkd2 , Ift88 , and Double Mutant Mouse Models. Journal of the American Society of Nephrology : JASN 2 40455584
2025 UFL1-mediated UFMylation antagonizes IFT88 ubiquitination and degradation to maintain ciliary homeostasis. Cell death and differentiation 2 41272290
2024 T cell-expressed Ift88 is required for proper thymocyte differentiation in mice. Physiological reports 2 39562155
2019 Distinct Activities of Gli1 and Gli2 in the Absence of Ift88 and the Primary Cilia. Journal of developmental biology 2 30791390
2026 Inducible Ift88-deficient mice show features consistent with mild pulmonary hypertension. Physiological reports 1 41588821
2022 The Relationship between Ultrasonographic Features of Hepatocellular Carcinoma and the Severity of Hepatocellular Carcinoma and the Expression of PTEN and Tg737. Journal of healthcare engineering 1 35368955
2021 Ift88, but not Kif3a, is required for establishment of the periciliary membrane compartment. Biochemical and biophysical research communications 1 34753064
2026 IFT88/Kindlin-2 Signaling Prevents Mechanical Overloading-Induced PANoptosis of Nucleus Pulposus Cells by Activating FOXP1 SUMOylation. International journal of biological sciences 0 42157928
2026 The protein turnover and trafficking of Chlamyopsin6 is regulated by IFT88 and IFT52 in the Chlamydomonas reinhardtii. Biochemical and biophysical research communications 0 42214917
2025 Functionally Essential and Structurally Diverse: Insights into the zebrafish Left-Right Organizer's Cilia via Optogenetic IFT88 Perturbation and Volume Electron Microscopy. bioRxiv : the preprint server for biology 0 40964258
2025 Mutations in CFAP57 disrupt the localization of MYH10 and IFT88, leading to flagellogenesis failure in humans and mice. Human genomics 0 41466333
2024 Temporal Ablation of the Ciliary Protein IFT88 Alters Normal Brainwave Patterns. bioRxiv : the preprint server for biology 0 38617207
2023 Retracted: The Relationship between Ultrasonographic Features of Hepatocellular Carcinoma and the Severity of Hepatocellular Carcinoma and the Expression of PTEN and Tg737. Journal of healthcare engineering 0 37829384

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