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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LACTB
lactamase beta
Chromosome 15 · 15q22.2
NCBI Gene: 114294Ensembl: ENSG00000103642.12HGNC: HGNC:16468UniProt: P83111
98PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
ProteaseTumor Suppressor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
proteolysispeptidase activityregulation of lipid metabolic processmitochondrionlymphatic system diseasegastric cancermelanomacolorectal carcinoma
✦AI Summary

LACTB is a mitochondrial serine protease that functions as a multifaceted regulator of cellular metabolism and apoptosis. As a mitochondrial intermembrane space protein, LACTB assembles into ordered filaments that enhance its catalytic activity 1. Primary functions include regulating mitochondrial lipid metabolism by decreasing PISD protein levels and affecting phosphatidylserine conversion 2, and cleaving phospholipase A2 group VI (PLA2G6) to modulate oxidized phospholipid metabolism 3. Mechanistically, LACTB influences cancer progression through multiple pathways: it promotes ferroptosis by blocking HSPA8 transcription and inhibiting GSH/GPX4 signaling 4, triggers apoptosis through inner mitochondrial membrane remodeling and cardiolipin-enriched membrane binding 5, and suppresses migration via RHOC/Cofilin pathway downregulation 6. Post-translational modification by OXCT1-mediated succinylation at K284 inhibits LACTB proteolytic activity, promoting hepatocellular carcinoma progression 7. Clinically, LACTB exhibits cancer-type-specific roles: it acts as a tumor suppressor in breast, lung, colorectal, and glioblastoma cancers through proliferation inhibition, but gains oncogenic function in osteosarcoma through M5L/R469K mutations that dysregulate p53 8. LACTB also protects against cardiovascular-kidney-metabolic syndrome through kidney-specific mechanisms 3, and serves as a lenvatinib target in liver cancer therapy 4.

Sources cited
1
LACTB regulates mitochondrial lipid metabolism by decreasing PISD protein levels
PMID: 28329758
2
LACTB assembles into filaments in the mitochondrial intermembrane space and increases catalytic activity through polymerization
PMID: 36534696
3
LACTB cleaves and activates PLA2G6 to regulate oxidized phospholipid metabolism and protect against kidney-metabolic disorders
PMID: 39561766
4
LACTB promotes ferroptosis in liver cancer by blocking HSPA8 transcription and inhibiting GSH/GPX4 signaling
PMID: 39047638
5
LACTB promotes apoptosis through inner mitochondrial membrane remodeling and cardiolipin-enriched membrane binding
PMID: 41223265
6
LACTB suppresses glioblastoma migration and invasion via RHOC/Cofilin signaling pathway downregulation
PMID: 36088805
7
OXCT1-mediated succinylation at LACTB K284 inhibits proteolytic activity and promotes hepatocellular carcinoma
PMID: 38176415
8
LACTB M5L/R469K mutations confer oncogenic functions in osteosarcoma through p53 dysregulation
PMID: 39324579
Disease Associationsⓘ20
lymphatic system diseaseOpen Targets
0.24Weak
gastric cancerOpen Targets
0.10Weak
melanomaOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
neutropeniaOpen Targets
0.09Suggestive
Decreased total leukocyte countOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.08Suggestive
gliomaOpen Targets
0.08Suggestive
colorectal cancerOpen Targets
0.08Suggestive
pancreatic adenocarcinomaOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.08Suggestive
lung cancerOpen Targets
0.08Suggestive
liver cancerOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
alcohol drinkingOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.06Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.05Suggestive
X-linked retinal dysplasiaOpen Targets
0.05Suggestive
osteosarcomaOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_032857.5(LACTB):c.785_786del (p.Phe262fs)Pathogenic
Hypercholesterolemia, familial, 1
☆☆☆☆2022→ Residue 262
View on ClinVar ↗
Related Genes
NSFL1CProtein interaction99%UBXN2AProtein interaction99%PPM1LProtein interaction89%INTS9Protein interaction77%PGA4Shared pathway50%PGA3Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Heart
85%
Lung
83%
Bone Marrow
83%
Brain
34%
Ovary
23%
Gene Interaction Network
Click a node to explore
LACTBNSFL1CUBXN2APPM1LINTS9PGA4PGA3
PROTEIN STRUCTURE
Preparing viewer…
PDB7V1Y · 2.82 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.05LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.76 [0.56–1.05]
RankingsWhere LACTB stands among ~20K protein-coding genes
  • #4,890of 20,598
    Most Researched98 · top quartile
  • #4,894of 5,498
    Most Pathogenic Variants1
  • #10,455of 17,882
    Most Constrained (LOEUF)1.05
Genes detectedLACTB
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
OXCT1 functions as a succinyltransferase, contributing to hepatocellular carcinoma via succinylating LACTB.
PMID: 38176415
Mol Cell · 2024
1.00
2
Human genetics identify convergent signals in mitochondrial LACTB-mediated lipid metabolism in cardiovascular-kidney-metabolic syndrome.
PMID: 39561766
Cell Metab · 2025
0.90
3
LACTB suppresses liver cancer progression through regulation of ferroptosis.
PMID: 39047638
Redox Biol · 2024
0.80
4
SNPs Give LACTB Oncogene-Like Functions and Prompt Tumor Progression via Dual-Regulating p53.
PMID: 39324579
Adv Sci (Weinh) · 2024
0.70
5
The structure of the human LACTB filament reveals the mechanisms of assembly and membrane binding.
PMID: 36534696
PLoS Biol · 2022
0.60