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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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STK25
serine/threonine kinase 25
Chromosome 2 · 2q37.3
NCBI Gene: 10494Ensembl: ENSG00000115694.16HGNC: HGNC:11404UniProt: A0A024R4B2
87PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Golgi apparatusGolgi localizationestablishment of Golgi localizationGolgi reassemblyAlzheimer diseaseParkinson diseaseneurodegenerative diseaselysosomal storage disease
✦AI Summary

STK25 is a serine/threonine kinase that functions as a critical regulator of cellular metabolic homeostasis and stress responses. As part of STRIPAK complexes, STK25 participates in multiple signaling pathways including Hippo, MAPK, and inflammatory signaling 1. The kinase localizes to the Golgi apparatus where it regulates protein transport, cell polarity, and migration 2. Mechanistically, STK25 responds to oxidative stress and metabolic signals to control lipid storage and glucose homeostasis 2. During alcohol-associated liver disease, STK25 inhibits PKA activity through phosphorylation, suppressing fatty acid oxidation and promoting hepatic steatosis 3. In immune cells, STK25 phosphorylates IRF5 at Thr265, promoting pro-inflammatory cytokine production downstream of TLR signaling 4. STK25 also regulates the Hippo pathway by phosphorylating LATS1/2, controlling YAP activation 5. Clinically, STK25 elevation associates with multiple diseases. High STK25 expression correlates with atherosclerosis progression 6, colorectal cancer development 7, and systemic lupus erythematosus 4. STK25 knockout enhances anti-PD-1 immunotherapy efficacy by increasing PD-L1 stability 7, positioning STK25 inhibition as a therapeutic strategy for metabolic disorders, atherosclerosis, autoimmune diseases, and cancer immunotherapy resistance.

Sources cited
1
STK25 is part of STRIPAK complexes with roles in protein phosphorylation and regulation of multiple signaling pathways including Hippo, MAPK, and cytoskeleton remodeling
PMID: 18782753
2
STK25 is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, and participates in autophagy, cell polarity, apoptosis, and migration
PMID: 36728989
3
STK25 inhibits PKA activity and promotes lipid accumulation in hepatocytes during alcohol-associated liver disease by reducing PKA-mediated phosphorylation of lipogenic enzymes
PMID: 40199859
4
STK25 silencing in aortic endothelial and smooth muscle cells reduces lipid accumulation and suppresses inflammatory and fibrotic pathways, making it atheroprotective
PMID: 35440683
5
STK25 phosphorylates IRF5 at Thr265 downstream of TLR-MyD88 signaling to promote pro-inflammatory cytokine production, and STK25 autophosphorylation is elevated in systemic lupus erythematosus patients
PMID: 40639948
6
STK25 knockout enhances anti-PD-1 therapy efficacy by regulating PD-L1 protein stability, and CRC patients with low STK25 expression are more responsive to immune checkpoint blockade
PMID: 40729594
7
STK25-mediated phosphorylation of LATS1/2 controls YAP activation in the Hippo pathway, preventing colorectal cancer progression
PMID: 39915446
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.28Weak
Parkinson diseaseOpen Targets
0.27Weak
lysosomal storage diseaseOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.27Weak
aortic diseaseOpen Targets
0.25Weak
liver diseaseOpen Targets
0.25Weak
Abnormality of the skeletal systemOpen Targets
0.16Weak
osteoarthritisOpen Targets
0.16Weak
type 1 diabetes mellitusOpen Targets
0.15Weak
hepatocellular carcinomaOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.08Suggestive
hypothyroidismOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
liver cancerOpen Targets
0.07Suggestive
osteoarthritis, hipOpen Targets
0.06Suggestive
hypertensionOpen Targets
0.06Suggestive
HerniaOpen Targets
0.06Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.05Suggestive
prostate carcinomaOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
STRADAProtein interaction100%STRIP1Protein interaction100%STRN3Protein interaction100%STRIP2Protein interaction100%MOB4Protein interaction100%TRAF3IP3Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Lung
92%
Liver
90%
Heart
86%
Bone Marrow
73%
Brain
60%
Gene Interaction Network
Click a node to explore
STK25STRADASTRIP1STRN3STRIP2MOB4TRAF3IP3
PROTEIN STRUCTURE
Preparing viewer…
PDB7Z4V · 1.64 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.70LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.52 [0.38–0.70]
RankingsWhere STK25 stands among ~20K protein-coding genes
  • #5,518of 20,598
    Most Researched87
  • #5,372of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedSTK25
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Novel vectors and approaches for gene therapy in liver diseases.
PMID: 34159305
JHEP Rep · 2021
1.00
2
STK25: a viable therapeutic target for cancer treatments?
PMID: 36728989
Anticancer Drugs · 2023
0.90
3
The AKAP12-PKA axis regulates lipid homeostasis during alcohol-associated liver disease.
PMID: 40199859
Signal Transduct Target Ther · 2025
0.80
4
Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective.
PMID: 35440683
Commun Biol · 2022
0.70
5
STK25 Loss Augments Anti-PD-1 Therapy Efficacy by Regulating PD-L1 Stability in Colorectal Cancer.
PMID: 40729594
Adv Sci (Weinh) · 2025
0.60