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29 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLPI
secretory leukocyte peptidase inhibitor
Chromosome 20 · 20q13.12
NCBI Gene: 6590Ensembl: ENSG00000124107.5HGNC: HGNC:11092UniProt: P03973
170PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular matrixDNA bindingmRNA bindingendopeptidase inhibitor activityAbnormal male internal genitalia morphologyneoplasmhepatocellular carcinomacardiovascular disease
✦AI Summary

SLPI (secretory leukocyte peptidase inhibitor) is a multifunctional serine protease inhibitor with broad biological roles in immunity and tissue homeostasis. SLPI contains a whey acidic protein (WAP) domain that enables potent inhibition of neutrophil serine proteases including elastase, cathepsin G, and proteinase 3 1. Beyond protease inhibition, SLPI exhibits antimicrobial activity against mycobacteria and modulates inflammatory responses by suppressing NF-κB-mediated gene transcription in response to bacterial lipopolysaccharide 23. SLPI expression is upregulated by pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and plays critical roles in tissue repair and wound healing by limiting protease-induced damage 45. In inflammatory lung diseases such as cystic fibrosis and COPD, SLPI protects airways from neutrophil-derived proteolytic damage while controlling excessive inflammation 6. Recent evidence reveals that α2-adrenergic signaling drives pathological SLPI production in cartilage, promoting hypertrophic degeneration and contributing to osteoarthritis progression; SLPI deletion prevents this cartilage degeneration 7. Additionally, while SLPI's anti-inflammatory and antimicrobial functions protect mucosal barrier tissues, excessive expression may promote epithelial tumor metastasis 8. These diverse functions position SLPI as a promising therapeutic target across multiple disease contexts.

Sources cited
1
SLPI inhibits neutrophil serine proteases (elastase, proteinase 3, cathepsin G) via WAP domain and has anti-bacterial, anti-fungal, anti-viral, and immuno-modulatory functions
PMID: 17964057
2
SLPI modulates responses to LPS and suppresses inflammatory gene expression, playing important roles in innate immune system function
PMID: 16336202
3
SLPI protects airways from proteolytic damage and interferes with NF-κB-mediated pro-inflammatory gene expression in inflammatory lung disease
PMID: 21936826
4
SLPI is augmented by pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and plays crucial roles in joint homeostasis and tissue repair
PMID: 40723781
5
SLPI exhibits anti-apoptotic activity, regulates cell cycle and differentiation, and enhances phagocytic clearance of pathogens and damaged cells
PMID: 38939941
6
SLPI has therapeutic potential for reducing protease-induced inflammatory responses in chronic lung diseases like cystic fibrosis and COPD
PMID: 21936830
7
α2-adrenergic signaling induces SLPI production that promotes cartilage hypertrophic degeneration; SLPI deletion prevents cartilage degeneration
PMID: 39353427
8
While SLPI protects mucosal tissues from inflammation and infection, excessive expression in cancer cells increases metastatic potential of epithelial tumors
PMID: 33602652
Disease Associationsⓘ20
Abnormal male internal genitalia morphologyOpen Targets
0.18Weak
neoplasmOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.11Weak
cardiovascular diseaseOpen Targets
0.11Weak
strokeOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.10Weak
infectionOpen Targets
0.10Weak
metabolic syndromeOpen Targets
0.10Suggestive
Alzheimer diseaseOpen Targets
0.10Suggestive
chronic kidney diseaseOpen Targets
0.10Suggestive
cancerOpen Targets
0.10Suggestive
osteoporosisOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.09Suggestive
Parkinson diseaseOpen Targets
0.09Suggestive
colorectal cancerOpen Targets
0.09Suggestive
head and neck squamous cell carcinomaOpen Targets
0.09Suggestive
bacteriemiaOpen Targets
0.09Suggestive
Marchiafava-Bignami DiseaseOpen Targets
0.09Suggestive
acute myeloid leukemiaOpen Targets
0.09Suggestive
hypertensionOpen Targets
0.09Suggestive
Pathogenic Variants1
NM_003064.4(SLPI):c.394+1G>TPathogenic
Otitis media, susceptibility to
★☆☆☆2023
View on ClinVar ↗
Related Genes
GRNProtein interaction93%CTRB1Protein interaction89%CTSGProtein interaction89%ELANEProtein interaction89%LTFProtein interaction89%DEFB103AProtein interaction84%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
24%
Liver
23%
Heart
1%
Ovary
0%
Brain
0%
Gene Interaction Network
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SLPIGRNCTRB1CTSGELANELTFDEFB103A
PROTEIN STRUCTURE
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PDB2Z7F · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.79LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.28 [0.89–1.79]
RankingsWhere SLPI stands among ~20K protein-coding genes
  • #2,609of 20,598
    Most Researched170 · top quartile
  • #4,755of 5,498
    Most Pathogenic Variants1
  • #16,529of 17,882
    Most Constrained (LOEUF)1.79
Genes detectedSLPI
Sources retrieved29 papers
Response time—
📄 Sources
29▼
1
A human organoid drug screen identifies α2-adrenergic receptor signaling as a therapeutic target for cartilage regeneration.
PMID: 39353427
Cell Stem Cell · 2024
1.00
2
Vitamin D deficiency induces erectile dysfunction: Role of superoxide and Slpi.
PMID: 40222751
Br J Pharmacol · 2025
0.92
3
Multifaceted roles of human elafin and secretory leukocyte proteinase inhibitor (SLPI), two serine protease inhibitors of the chelonianin family.
PMID: 17964057
Biochimie · 2008
0.90
4
Structure of the murine secretory leukoprotease inhibitor (Slpi) gene and chromosomal localization of the human and murine SLPI genes.
PMID: 9843921
Am J Respir Cell Mol Biol · 1998
0.88
5
Reduced ELANE and SLPI expression compromises dental pulp cell activity.
PMID: 34580954
Cell Prolif · 2021
0.84