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Last update 08 May 2025

LIPA

Last update 08 May 2025

Basic Info

Synonyms

Acid cholesteryl ester hydrolase, CESD, Cholesteryl esterase

+ [6]

Introduction

Catalyzes the deacylation of cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol (PubMed:15269241, PubMed:1718995, PubMed:7204383, PubMed:8112342, PubMed:9633819). Hydrolyzes triglycerides (1,2,3-triacylglycerol) and diglycerides (such as 1,2-diacylglycerol and 1,3-diacylglycerol) with preference for the acyl moieties at the sn-1 or sn-3 positions (PubMed:7204383, PubMed:8112342).

Drugs associated with LIPA

Sebelipase Alfa

Target

LIPA

Mechanism

LIPA modulators

Active Org.

AstraZeneca PLC [+5]

Originator Org.

Alexion Pharmaceuticals, Inc.

Active Indication

Cholesterol Ester Storage Disease [+1]

Inactive Indication

Failure to Thrive [+2]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

European Union [+3]

First Approval Date28 Aug 2015

ERX-315

Target

LIPA

Mechanism

LIPA modulators

Active Org.

The University of Texas at Dallas [+3]

Originator Org.

EtiraRx LLC

Active Indication

Advanced Malignant Solid Neoplasm [+6]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

LIPA cDN AAV gene therapy(Genethon)

Target

LIPA

Mechanism

LIPA modulators

Active Org.

Genethon

Originator Org.

Genethon

Active Indication

Wolman Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with LIPA

NCT06533332

/ RecruitingPhase 1

A First-in-Human, Phase 1 Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy Study of Escalating Doses of ERX-315 in Participants With Advanced Solid Tumors

This is a Phase 1 study to assess the safety of ERX-315 in patients with advanced solid tumors that have failed approved systemic therapies.

Start Date14 Oct 2024

Sponsor / Collaborator-

EUCTR2014-000533-22-FI

/ Not yet recruitingPhase 2

A Phase 2, Open Label, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Sebelipase Alfa in Infants with Rapidly Progressive Lysosomal Acid Lipase Deficiency

Start Date23 Jun 2015

Sponsor / Collaborator

Alexion Pharmaceuticals, Inc.

NCT02112994

/ CompletedPhase 2

A Multi-Center, Open-Label Study of Sebelipase Alfa in Patients With Lysosomal Acid Lipase Deficiency

This study evaluated the safety and efficacy of sebelipase alfa in a broad population of participants with lysosomal acid lipase deficiency (LAL-D).

Start Date24 Jun 2014

Sponsor / Collaborator

Alexion Pharmaceuticals, Inc.

100 Clinical Results associated with LIPA

100 Translational Medicine associated with LIPA

0 Patents (Medical) associated with LIPA

1,134

Literatures (Medical) associated with LIPA

01 Jun 2025·Prostaglandins & Other Lipid Mediators

GLP-1RAs regulate lipid metabolism and induce autophagy through AMPK/SIRT1 pathway to improve NAFLD

Article

Author: Wang, Jingyuan ; Hu, Xiaojin ; Yue, Hongqin ; Zhang, Qiang ; Cao, Yang ; Niu, Chunyan ; Lu, Wei

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is a leading cause of cirrhosis and a major risk factor for hepatocellular carcinoma and liver-related death. Diabetes medications have been studied as potential treatments for NAFLD. Glucagon-like peptide-1 agonists (GLP-1RAs) have been rarely reported in the treatment of NAFLD alone as an anti-diabetic drug, and its specific mechanism of action is unknown. We investigated whether the therapeutic effect of liraglutide (LRG, a representative drug of GLP-1RAs) on hepatic steatosis is related to regulating lipid metabolism and enhancing autophagy in the hepatocytes.METHODSWe examined the effect of LRG on fat accumulation in fatty hepatocytes, and discussed its effects on enzymes related to lipid metabolism and autophagy. Meanwhile, knockdown of SIRT1 in free fatty acids(FFA)-treated cells was used to detected the influence of LRG on lipid metabolism and autophagy by regulating of AMPK/SIRT1 signaling.RESULTSOur findings showed that free fatty acids (FFA) induced hepatocyte steatosis, which was significantly reversed by LRG. Meanwhile, LRG significantly regulated the expression of hepatocyte lipogenesis and cytosolic lipolysis-related proteins (FAS, ACC1, ATGL, HSL, LAL). Furthermore, LRG enhanced FFA-induced suppression of autophagy and SIRT1 expression, reducing intracellular lipid accumulation. It is evident that LRG regulates lipid metabolism and induces autophagy in an (AMPK)-dependent manner. Moreover, SIRT1 knockdown inhibited the autophagy-inducing and lipid-lowering effects of LRG.CONCLUSIONGLP-1RAs may lower hepatic steatosis by regulating lipid metabolism and enhancing autophagy in an AMPK/SIRT1-dependent manner, providing a new target for the treatment of NAFLD.

01 May 2025·International Journal of Biological Macromolecules

Formation of cross-linked lysinoalanine in soy protein isolate: Synergy between hot-alkali and pH-shift treatments

Article

Author: Song, Hanyu ; Yan, Shizhang ; Jiang, Lianzhou ; Liu, Yuwen ; Wu, Siyu ; Qi, Baokun

Combining hot-alkali and pH-shift (HS) treatments is a convenient and economical way of modifying proteins. However, the cross-linked lysinoalanine (LAL) formed during this process affects edible-protein safety. This study investigated the conformational changes experienced by soybean protein isolate (SPI) during HS treatment and the mechanism associated with LAL cross-linking. Heating at 75 °C for 1 h at pH 12.0 was shown to result in the highest amount of LAL cross-linking. Reactive-group and spectral data revealed that HS treatment led to breakage of the internal disulfide bonds in SPI, as well as subunit depolymerization and collapse, with the highly disordered and flexible conformation of SPI eventually providing a favorable spatial effect for LAL cross-linking. Gel electrophoresis, particle size and ζ-potential analyses, SEM, and AFM revealed that thermal aggregation not only protects the SPI conformation against damage caused by extreme alkalinity, but also accelerates the rate of LAL cross-linking. In addition, the various SPI structures and the formation of cross-linked LAL were found to be strongly correlated (|r| > 0.7). This study clarified the synergistic mechanism associated with heat-alkali and pH-shift treatments that promote SPI conformational modifications and LAL cross-linking, and provides a theoretical basis for controlling the formation of LAL and improving the edible safety of SPI.

01 May 2025·International Journal of Biological Macromolecules

Integrating protein contact networks for the engineering of thermostable lipase A

Article

Author: Tian, Siyuan ; Hu, Mingzhu ; Fang, Ruijie ; Ding, Jian ; Lu, Cheng ; Wang, Jianan

In the field of industrial biocatalysis, the rapid advancement of enzyme functional evolution necessitates new theories and computational methods to achieve target functions with fewer iterations. This study identified key residues affecting enzyme stability by constructing the protein contact network (PCN) of Lipase A. Comparing the PCNs of the wild-type (WT) and the 6B variant revealed that changes in residue interactions and node properties (e.g., degree and betweenness centrality (BC)) positively impacted stability. Using thresholds for degree and BC, 25 candidate sites were screened, and 11 out of 18 single-point mutation designs improved thermal stability. Mutations were divided into three groups (M1, M2, M3) based on network communities and contributions, followed by iterative combinations. M1, containing five mutations distributed across four communities, increased the melting temperature (T_m) by 14.61 °C, close to the predicted 13.97 °C, demonstrating a linear additive effect. In M2, three new mutations resulted in a non-linear additive effect, with a ΔT_m of 17.58 °C (Expected ΔT_m = 18.93 °C). In contrast, the three new mutations in M3 destabilized the enzyme (Observed ΔT_m = 15.94 °C vs Expected ΔT_m = 19.92 °C). Molecular dynamics simulations showed that polar edge nodes enhanced network connectivity, while proline mutations rigidified flexible regions, improving stability. Conversely, M3 mutations disrupted α-helix stability by increasing the dihedral angle fluctuations of residue Y161, might to a stability-activity trade-off. The PCN provides valuable insights for developing efficient and precise design strategies.

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