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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KLK8
kallikrein related peptidase 8
Chromosome 19 · 19q13.41
NCBI Gene: 11202Ensembl: ENSG00000129455.16HGNC: HGNC:6369UniProt: A0A0A0MQY9
60PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
serine-type endopeptidase activityserine protease inhibitor complexcytoplasmprotein bindingactinic keratosisAlzheimer diseasedepressive disorderinfection
✦AI Summary

KLK8 (kallikrein related peptidase 8) is a secreted serine protease with diverse physiological functions across multiple tissues. In the nervous system, KLK8 plays a critical role in synaptic plasticity and memory formation, with knockout mice showing suppressed long-term potentiation in the hippocampus 1. The protein cleaves pro-HGF to activate the HGF/Met signaling pathway, which can mediate neuroinflammation in diabetic conditions, contributing to depression-like behaviors 2. In skin biology, KLK8 functions in keratinocyte proliferation and desquamation through degradation of adhesive molecules connecting epidermal layers 1, with its expression strongly correlating with keratinocyte proliferation marker MKI67 in wound healing 3. KLK8 also drives pathological processes, including diabetic cardiac fibrosis through endothelial-to-mesenchymal transition mediated by VE-cadherin cleavage and TGF-β1 signaling 4. In psoriasis, KLK8 creates a positive feedback loop with IL-17A signaling, promoting histone H4K12 lactylation and keratinocyte hyperproliferation 5. Clinically, KLK8 serves as a favorable prognostic marker in ovarian cancer, with higher expression associated with longer disease-free survival 6. The protein's multifunctional nature reflects its tissue-specific roles in both physiological processes and disease pathogenesis.

Sources cited
1
KLK8 knockout mice show suppressed hippocampal long-term potentiation and KLK8 involvement in skin desquamation
PMID: 20180635
2
KLK8 cleaves pro-HGF to activate HGF/Met signaling pathway mediating diabetes-associated neuroinflammation
PMID: 40521191
3
KLK8 expression strongly correlates with MKI67 mRNA levels as potential biomarker for keratinocyte proliferation
PMID: 36555389
4
KLK8 mediates diabetic cardiac fibrosis through VE-cadherin cleavage and endothelial-to-mesenchymal transition
PMID: 33754057
5
KLK8 creates positive feedback loop with IL-17A signaling promoting histone H4K12 lactylation in psoriasis
PMID: 41027887
6
Higher KLK8 expression serves as favorable prognostic marker associated with longer disease-free survival in ovarian cancer
PMID: 11309326
Disease Associationsⓘ20
actinic keratosisOpen Targets
0.31Weak
Alzheimer diseaseOpen Targets
0.10Weak
depressive disorderOpen Targets
0.10Suggestive
infectionOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
melanomaOpen Targets
0.08Suggestive
influenzaOpen Targets
0.08Suggestive
psoriasisOpen Targets
0.07Suggestive
cardiac hypertrophyOpen Targets
0.06Suggestive
cancerOpen Targets
0.05Suggestive
diabetes mellitusOpen Targets
0.05Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
HyperkeratosisOpen Targets
0.05Suggestive
Parkinson diseaseOpen Targets
0.04Suggestive
COVID-19Open Targets
0.04Suggestive
immunodeficiency 84Open Targets
0.04Suggestive
acute erythroleukemiaOpen Targets
0.04Suggestive
erythroleukemia, familial, susceptibility toOpen Targets
0.04Suggestive
combined immunodeficiency due to OX40 deficiencyOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SPINK9Protein interaction99%KLK7Protein interaction95%KLK5Protein interaction95%CARD16Protein interaction90%CASP1Protein interaction76%SERPINA5Protein interaction73%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
100%
Lung
100%
Brain
50%
Liver
50%
Heart
0%
Gene Interaction Network
Click a node to explore
KLK8SPINK9KLK7KLK5CARD16CASP1SERPINA5
PROTEIN STRUCTURE
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PDB5MS4 · 2.10 Å · X-ray
View on RCSB ↗
RankingsWhere KLK8 stands among ~20K protein-coding genes
  • #7,679of 20,598
    Most Researched60
Genes detectedKLK8
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Gene Expression Linked to Reepithelialization of Human Skin Wounds.
PMID: 36555389
Int J Mol Sci · 2022
1.00
2
KLK8/HGF/Met signaling pathway mediates diabetes-associated hippocampal neuroinflammation in male mice.
PMID: 40521191
Theranostics · 2025
0.90
3
A novel role of kallikrein-related peptidase 8 in the pathogenesis of diabetic cardiac fibrosis.
PMID: 33754057
Theranostics · 2021
0.80
4
Keratinocyte-specific H4K12 lactylation drives a non-canonical IL-17-dependent signaling in psoriasis progression in mice.
PMID: 41027887
Nat Commun · 2025
0.70
5
The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice variants and its prognostic value in ovarian cancer.
PMID: 11309326
Clin Cancer Res · 2001
0.60