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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LNPEP
leucyl and cystinyl aminopeptidase
Chromosome 5 · 5q15
NCBI Gene: 4012Ensembl: ENSG00000113441.17HGNC: HGNC:6656UniProt: Q9UIQ6
122PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membraneaminopeptidase activitymembranelysosomal membraneinflammatory bowel diseasefrozen shoulderCrohn's diseasehypertension
✦AI Summary

LNPEP (leucyl and cystinyl aminopeptidase) is a membrane-bound zinc-dependent metalloexopeptidase that functions primarily in the degradation of peptide hormones including oxytocin, vasopressin, and angiotensin IV 1. The enzyme cleaves N-terminal amino acids, particularly before cysteine and leucine residues, and plays a crucial role in maintaining homeostasis during pregnancy through vasopressin inactivation 1. LNPEP is regulated by insulin and colocalizes with GLUT4 in muscle and adipose tissue, where it terminates vasopressin activity at the cell surface 1. Beyond hormone regulation, LNPEP contributes to antigen processing and presentation, particularly in cross-presentation pathways, with expression predominantly in granular layer keratinocytes for processing extracellular antigens 2. The enzyme shows evolutionary conservation across vertebrates, with evidence suggesting its expression in the hypothalamus correlates with behavioral social status in fish 3. Clinically, LNPEP dysfunction is linked to gestational diabetes insipidus and preeclampsia, while its role in accelerated vasopressin degradation during insulin resistance may contribute to hypertension in metabolic syndrome 1. Recent studies also implicate LNPEP in renin-angiotensin system regulation and potential therapeutic targets in cardiovascular disease 4.

Sources cited
1
LNPEP is a zinc-dependent metalloexopeptidase that degrades vasopressin and oxytocin, regulated by insulin and involved in gestational diabetes and metabolic syndrome
PMID: 32138946
2
LNPEP is expressed in granular layer keratinocytes and specializes in processing extracellular antigens for T cell presentation
PMID: 36716917
3
LNPEP shows evolutionary conservation and hypothalamic expression correlates with behavioral social status in vertebrates
PMID: 28596078
4
LNPEP is upregulated in hypertension and involved in renin-angiotensin system regulation as a potential therapeutic target
PMID: 40907688
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
inflammatory bowel diseaseOpen Targets
0.27Weak
frozen shoulderOpen Targets
0.25Weak
Crohn's diseaseOpen Targets
0.24Weak
hypertensionOpen Targets
0.22Weak
HypercholesterolemiaOpen Targets
0.22Weak
response to xenobiotic stimulusOpen Targets
0.22Weak
lichen planusOpen Targets
0.18Weak
substance abuseOpen Targets
0.16Weak
attention deficit hyperactivity disorderOpen Targets
0.16Weak
neoplasmOpen Targets
0.12Weak
acute myeloid leukemiaOpen Targets
0.10Suggestive
myelodysplastic syndromeOpen Targets
0.10Suggestive
infectionOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
cancerOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
strokeOpen Targets
0.07Suggestive
type 1 diabetes mellitusOpen Targets
0.07Suggestive
acute myeloid leukemia by FAB classificationOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
TOSEDOSTATPhase II
Aminopeptidase inhibitor
acute myeloid leukemia by FAB classification
Related Genes
TBC1D4Protein interaction98%TNKS2Protein interaction91%SLC2A4Protein interaction90%TNKSProtein interaction89%LIX1Protein interaction87%OXTProtein interaction87%
Tissue Expression6 tissues
Heart
100%
Brain
66%
Bone Marrow
50%
Lung
45%
Ovary
44%
Liver
25%
Gene Interaction Network
Click a node to explore
LNPEPTBC1D4TNKS2SLC2A4TNKSLIX1OXT
PROTEIN STRUCTURE
Preparing viewer…
PDB5MJ6 · 2.53 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.61LoF Tolerant
pLIⓘ
0.05Tolerant
Observed/Expected LoF0.44 [0.32–0.61]
RankingsWhere LNPEP stands among ~20K protein-coding genes
  • #3,856of 20,598
    Most Researched122 · top quartile
  • #4,200of 17,882
    Most Constrained (LOEUF)0.61 · top quartile
Genes detectedLNPEP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The role of LNPEP and ANPEP gene polymorphisms in the pathogenesis of pre-eclampsia.
PMID: 32619880
Eur J Obstet Gynecol Reprod Biol · 2020
1.00
2
Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.
PMID: 36716917
J Invest Dermatol · 2023
0.90
3
Vasopressin inactivation: Role of insulin-regulated aminopeptidase.
PMID: 32138946
Vitam Horm · 2020
0.80
4
The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease.
PMID: 32793222
Front Immunol · 2020
0.70
5
From molecular variations to behavioral adaptations: Unveiling adaptive epistasis in primate oxytocin system.
PMID: 38783700
Am J Biol Anthropol · 2024
0.60