ArticleNature2014
RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 343 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
343 citing papers in PubMed, 1 synthesis or guideline pooled it, 544 citations in OpenAlex.
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- Early Development of Ocadusertib, a Selective Receptor-Interacting Serine/Threonine-Protein Kinase 1 Inhibitor.Clinical and translational science · 2026Trial
- Rhaponticin alleviates pancreatic acinar cell necrosis by attenuating oxidative stress via modulation of the HIF-1α signaling pathway.Redox report : communications in free radical research · 2026Article
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Human ZBP1 is a potent inducer of cell death through mechanisms divergent from mouse ZBP1.EMBO reports · 2026Article
- The dual role of RIPK family in IBD: from cell death to therapeutic targeting.Molecular medicine (Cambridge, Mass.) · 2026Review
- Hyperlipidemia induces hippocampal inflammation and loss of vascularity and can be rescued by silencing RIPK1.Scientific reports · 2026Article
- Metastable Protein-Protein Interactions as a Design Principle for PROTACs: Insights from the RIPK1-VHL System.JACS Au · 2026Article
- Arginine Di-methylation of RIP3 safeguards necroptosis for intestinal homeostasis.Cell death and differentiation · 2026Article
- Nanovaccines with ferroptosis, necroptosis and STING-activation for synergistic immunotherapy.Journal of experimental & clinical cancer research : CR · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Type I and III interferons synergize with TNF to promote virally-triggered damage to the intestinal epithelium.bioRxiv : the preprint server for biology · 2026Article
- Bioorthogonal catalytic centres engineered for gastrointestinal stabilization provide oral delivery for the treatment of gastric cancer.Journal of nanobiotechnology · 2026Article
- cGAS-IFN-I responses by extracting nuclear DNA from dying cells via nucleocytosis.Nature communications · 2026Article
- The landscape of regulated cell death: It's all downhill from here.Molecular cell · 2026Review
- Programmed cell death of keratinocytes: an active driver in psoriasis.Apoptosis : an international journal on programmed cell death · 2026Review
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Research progress on targeted regulatory proteins in the prevention and treatment of atherosclerosis.Frontiers in immunology · 2026Review
283 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Necroptosis has emerged as an important pathway of programmed cell death in embryonic development, tissue homeostasis, immunity and inflammation. RIPK1 is implicated in inflammatory and cell death signalling and its kinase activity is believed to drive RIPK3-mediated necroptosis. Here we show that kinase-independent scaffolding RIPK1 functions regulate homeostasis and prevent inflammation in barrier tissues by inhibiting epithelial cell apoptosis and necroptosis. Intestinal epithelial cell (IEC)-specific RIPK1 knockout caused IEC apoptosis, villus atrophy, loss of goblet and Paneth cells and premature death in mice. This pathology developed independently of the microbiota and of MyD88 signalling but was partly rescued by TNFR1 (also known as TNFRSF1A) deficiency. Epithelial FADD ablation inhibited IEC apoptosis and prevented the premature death of mice with IEC-specific RIPK1 knockout. However, mice lacking both RIPK1 and FADD in IECs displayed RIPK3-dependent IEC necroptosis, Paneth cell loss and focal erosive inflammatory lesions in the colon. Moreover, a RIPK1 kinase inactive knock-in delayed but did not prevent inflammation caused by FADD deficiency in IECs or keratinocytes, showing that RIPK3-dependent necroptosis of FADD-deficient epithelial cells only partly requires RIPK1 kinase activity. Epidermis-specific RIPK1 knockout triggered keratinocyte apoptosis and necroptosis and caused severe skin inflammation that was prevented by RIPK3 but not FADD deficiency. These findings revealed that RIPK1 inhibits RIPK3-mediated necroptosis in keratinocytes in vivo and identified necroptosis as a more potent trigger of inflammation compared with apoptosis. Therefore, RIPK1 is a master regulator of epithelial cell survival, homeostasis and inflammation in the intestine and the skin.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.