ReviewFrontiers in pharmacology2025
MLKL as an emerging machinery for modulating organelle dynamics: regulatory mechanisms, pathophysiological significance, and targeted therapeutics.
Review in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Inorganic Arsenic Attenuates Crystalline Silica-Induced Pulmonary Inflammation and Fibrosis by Ameliorating Autophagolysosomal Dysfunction in Alveolar Macrophages.Biological trace element research · 2026Article
- A Non-Canonical Role for Hepatocyte MLKL in Promoting Mitochondrial Dysfunction and Senescence in the Aging Liver.Aging cell · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Cadmium targeting MLKL-Drp1 axis to trigger mitochondrial oxidative stress contributes to necroinflammation in rat kidney.Journal of advanced research · 2026Article
- Metabolic syndrome necroptosis: disease implications and therapeutic targeting.Journal of physiology and biochemistry · 2026Review
- MLKL in liver parenchymal cells promotes liver cancer in murine metabolic dysfunction-associated steatotic liver disease.Cell death & disease · 2026Article
- RIP3 and MLKL regulate ER stress in alcohol-associated liver disease and pharmacological ER stress models: Insights beyond necroptosis.JHEP reports : innovation in hepatology · 2026Article
- A retrospective study comparing oral celecoxib combined with flurbiprofen hydrogel patch versus oral celecoxib therapy for lateral epicondylitis: real-world analysis of the anti-inflammatory and analgesic efficacy and safety.Frontiers in pharmacology · 2026Article
- OTUD7B exacerbates atherosclerosis by promoting RIPK1-dependent vascular smooth muscle cell necroptosis.Frontiers in cardiovascular medicine · 2026Article
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- The Immunoregulatory Mechanisms of Human Cytomegalovirus from Primary Infection to Reactivation.Pathogens (Basel, Switzerland) · 2025Review
- RIP3 and MLKL regulate Hepatic ER stress in alcohol-associated liver disease and pharmacological ER stress models: insights beyond necroptosis.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mixed lineage kinase domain-like protein (MLKL) is a pseudokinase featured by a protein kinase-like domain without catalytic activity. MLKL was originally discovered to be phosphorylated by receptor-interacting protein kinase 1/3, typically increase plasma membrane permeabilization, and disrupt the membrane integrity, ultimately executing necroptosis. Recent evidence uncovers the association of MLKL with diverse cellular organelles, including the mitochondrion, lysosome, endosome, endoplasmic reticulum, and nucleus. Thus, this review mainly focuses on the regulatory functions, mechanisms, and targets of MLKL in organelles rather than necroptosis and summarize the medical significance in multiple diseases. On this basis, we conclude and analyze the current progress and prospect for the development of MLKL-related drugs, from natural products, small-molecule chemical compounds, to proteolysis-targeting chimera. This review is aimed to propel the development of MLKL as a valid drug target and the discovery of novel MLKL-related drugs, and promote their further applications.
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