ArticleScience advances2025
TRAM-LAG1-CLN8 family proteins are acyltransferases regulating phospholipid composition.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
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Who cites it
9 citing papers in PubMed.
- CLN8 recycles glycerol backbones for BMP.Nature cell biology · 2026Article
- Batten disease protein CLN8 enables a non-canonical phospholipid synthesis pathway.Nature cell biology · 2026Article
- The Batten disease protein CLN8 is a stereospecific acyltransferase in bis(monoacylglycero)phosphate biosynthesis.Nature cell biology · 2026Article
- A CLN8 biallelic missense variant causes epilepsy with severe treatment-resistant psychosis.Molecular genetics and genomics : MGG · 2026Article
- TLCD1 correlates with malignant progression of hepatocellular carcinoma and activation of the ERK signaling cascade.Scientific reports · 2026Article
- TRAM-LAG1-CLN8 domain-containing protein TMEM56 regulates cell migration by changing intracellular ceramide levels.BMC biology · 2026Article
- Review
- Lysosome heterogeneity and diversity mapped through its distinct cellular functions.Cellular and molecular life sciences : CMLS · 2025Review
- Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.Journal of the American Chemical Society · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The diversity of cellular phospholipids, crucial for membrane homeostasis and function, arises from enzymatic remodeling of their fatty acyl chains. In this work, we reveal that poorly understood TRAM-LAG1-CLN8 domain (TLCD)-containing proteins are phospholipid remodeling enzymes. We demonstrate that TLCD1 is an evolutionarily conserved lysophosphatidylethanolamine acyltransferase, which regulates cellular phospholipid composition and generates previously undescribed fatty acid and thiamine (vitamin B1) esters as its secondary products. Furthermore, we establish that human TLCD protein CLN8, mutations of which cause fatal neurodegenerative Batten disease, is a lysophosphatidylglycerol acyltransferase. We show that CLN8 catalyzes the essential step in the biosynthesis of bis(monoacylglycero)phosphate, a phospholipid critical for lysosome function. Our study unveils a family of acyltransferases integral to cellular membrane phospholipid homeostasis and human disease.
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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 Socratic graph.