Evidence map›Paper›PMID 41264248›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

DDHD2 possesses both lipase and transacylase capacities that remodel triglyceride acyl chains.

Lingshuang Wu, Yong Mi Choi, Mohyeddine Omrane, Jiyao Chai, Shujuan Gao, Abdou Rachid Thiam, Daniel Canals, Michael V Airola

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. The right environment switches the enzymatic character.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Lingshuang WuDepartment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook NY 11794.ORCID 0000-0002-3790-9010
Yong Mi ChoiDepartment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook NY 11794.
Mohyeddine OmraneLaboratoire de Physique de l'École Normale Supérieure, École Normale Supérieure, Université Paris Sciences et Lettres, CNRS, Sorbonne Université, Université Paris Cité, Paris F-75005, France.ORCID 0000-0002-0944-0462
Jiyao ChaiDepartment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook NY 11794.ORCID 0009-0009-7330-8368
Shujuan GaoDepartment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook NY 11794.ORCID 0000-0003-0735-1914
Abdou Rachid ThiamLaboratoire de Physique de l'École Normale Supérieure, École Normale Supérieure, Université Paris Sciences et Lettres, CNRS, Sorbonne Université, Université Paris Cité, Paris F-75005, France.ORCID 0000-0001-7488-4724
Daniel CanalsDepartment of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook NY 11794.ORCID 0000-0002-9293-5123
Michael V AirolaDepartment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook NY 11794.ORCID 0000-0003-4981-1253

Funding

Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI YUSUF AWNI HANNUN · 2003 to 2026
$30.8M
Structure and regulation of lipid metabolism and transportR35GM128666 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI Michael Virgil Airola · 2018 to 2026
$4.0M
Agence Nationale de la Recherche (ANR) ANR-21-CE13-0014-LIPDROPERAlfred P. Sloan Foundation (APSF) n/aAmerican Heart Association (AHA) 23PRE1019634HHS | NIH | National Institute of General Medical Sciences (NIGMS) R35GM128666NCI NIH HHS P01 CA097132NIGMS NIH HHS R35 GM128666SUNY | Stony Brook University (SBU) n/a
6 · The paper itself

Abstract

Hereditary spastic paraplegia subtype SPG54 is a genetic neurological disorder caused by mutations in the DDHD2 gene. Excessive lipid droplet accumulation is observed in the brains of SPG54 patients and DDHD2 knockout mice, consistent with DDHD2's reported neutral lipase activity. Here, we find recombinant human DDHD2 preferentially hydrolyzes diacylglycerol (DAG) over phospholipids, with a slight preference for DAG over triacylglycerol (TAG). DDHD2 also exhibits transacylase activity, which enables transfer of acyl chains from TAGs to DAGs and monoacylglycerols to remodel the acyl chains of TAGs. A predicted hydrophobic amphipathic helix on DDHD2 is essential for lipid droplet binding in vitro and in cells, and its lack reduces the enzymatic activity and TAG acyl chain remodeling. Adipose triglyceride lipase, but not hormone sensitive lipase, also has transacylation activity and can remodel TAG acyl chains, but to a lesser extent than DDHD2. Taken together, this provides evidence that DDHD2 is a neutral lipid lipase and transacylase whose broad specificity enables TAG acyl-chain remodeling.

Indexed as

AcyltransferasesLipaseTriglyceridesAcylationAnimalsDiglyceridesHumansLipid DropletsMiceMice, KnockoutSpastic Paraplegia, HereditarySubstrate SpecificityAcyltransferasesDiglyceridesLipaseTriglycerideslipaselipid dropletstransacylasetriglycerides

Identifiers

PMID41264248
PMCPMC12663969

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

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.