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Protein / target

Pancreatic triacylglycerol lipase

Encoded byPNLIPP16233Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Glycerophospholipid phospholipase A1

Strongest disease association

Pancreatic triacylglycerol lipase deficiency

Via encoding gene PNLIP · Genetic evidence · score 0.66

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Plays an important role in fat metabolism.

View complete UniProt function annotation

Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows considerably higher activity against insoluble emulsified substrates than against soluble ones

Subcellular location

Secreted
Domains and Gene Ontology detail (15)

Domains & features

PLAT

Gene Ontology

  • Cextracellular region
  • Cextracellular space
  • Fall-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity
  • Fglycerophospholipid phospholipase A1 activity
  • Flipase activity
  • Flipoprotein lipase activity
  • Fmetal ion binding
  • Ftriacylglycerol lipase activity
  • Pcholesterol homeostasis
  • Pfatty acid biosynthetic process
  • Phigh-density lipoprotein particle remodeling
  • Plipid metabolic process

465 aa · 51 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·Plays an important role in fat metabolism. It preferentially splits the esters of long-c…
  • ·glycerophospholipid phospholipase A1 activity
  • ·lipoprotein lipase activity
  • ·cholesterol homeostasis
View underlying pathways (3)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

CLPSLIPFPNLIPR…CELPNPLA2PNPLA3MGLLLIPCCTRB1LPLPNLIP

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

1 medicine · 1 area

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Obesity1 medicine

2 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

1

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

orlistat
Narrow target profileApprovedInhibitor

Pancreatic lipase inhibitor

Indicated for Obesity

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene PNLIP

Gene-level evidence surfaced through the gene PNLIPthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Obesity disorder
0.72Moderately supported

Clinical evidence dominant · Open Targets 0.58

Pancreatic triacylglycerol lipase deficiency
0.71Moderately supported

Genetic evidence dominant · Open Targets 0.55

Diabetes Mellitus, Type 2
0.51Moderately supported

Clinical evidence dominant · Open Targets 0.41

Respiratory Tract Infections
0.39Limited support

Genetic evidence dominant · Open Targets 0.24

Tooth disorder
0.25Limited support

Genetic evidence dominant · Open Targets 0.15

View evidence synthesis (5)
Obesity disorderModerately supported
0.72
agreement 0.560.87
Clinical91%Literature9%

Open Targets aggregate 0.58 · 2 independent evidence families

Pancreatic triacylglycerol lipase deficiencyModerately supported
0.71
agreement 0.590.83
Genetic81%Animal model17%Literature2%Genetic literaturedup

Open Targets aggregate 0.55 · 3 independent evidence families · 1 not counted as duplicate

Diabetes Mellitus, Type 2Moderately supported
0.51
agreement 0.350.66
Clinical96%Literature4%

Open Targets aggregate 0.41 · 2 independent evidence families

Respiratory Tract InfectionsLimited support
0.39
agreement 0.270.51
Genetic100%

Open Targets aggregate 0.24 · 1 independent evidence family

Tooth disorderLimited support
0.25
agreement 0.130.37
Genetic100%

Open Targets aggregate 0.15 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Obesity disorder0.58
Pancreatic triacylglycerol lipase deficiency0.55
Diabetes Mellitus, Type 20.41
Autoimmune disorder of central nervous system0.30
Respiratory Tract Infections0.24
Tooth disorder0.15
Familial lipoprotein lipase deficiency0.08

Drug development

2 compounds recorded · 2 approved

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 1 drug that targets this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (2)
ORLISTATApproval
CETILISTATApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

COMPLETED · via orlistat · NCT00212199

COMPLETED · via orlistat · NCT02767531

ClinicalTrials.gov via the drug-target graph.

What's happening now

7

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for a drug that targets this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2024-03-19
    Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis.

    European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2024 · 44 citations · Europe PMC · via orlistat

  2. Safety communication2014-12-11

    Drug Safety Update: Orlistat: theoretical interaction with antiretroviral HIV medicines

    mhra · safety · mhra · via orlistat

  3. New publication2010-01-01
    A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss.

    Archives of internal medicine · 2010 · 103 citations · Europe PMC · via orlistat

  4. Regulatory approval2007-07-22

    Approval: Alli (previously Orlistat GSK) (EMA)

    ema · regulatory · ema · via orlistat

  5. New publication2004-03-01
    Efficacy of orlistat as an adjunct to behavioral treatment in overweight African American and Caucasian adolescents with obesity-related co-morbid conditions.

    Journal of pediatric endocrinology & metabolism : JPEM · 2004 · 65 citations · Europe PMC · via orlistat

  6. New publication2002-07-01
    Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions.

    Obesity research · 2002 · 104 citations · Europe PMC · via orlistat

  7. Regulatory approval1998-07-29

    Approval: Xenical (EMA)

    ema · regulatory · ema · via orlistat

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Related family literature

5

Papers about “Lipase” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.

Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.