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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ROCK2
Rho associated coiled-coil containing protein kinase 2
Chromosome 2 · 2p25.1
NCBI Gene: 9475Ensembl: ENSG00000134318.17HGNC: HGNC:10252UniProt: A0A2P9DU05
308PubMed Papers
20Diseases
13Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinase
RESEARCH IMPACT
Trending
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of cell migrationcentrosomepositive regulation of amyloid precursor protein catabolic processregulation of establishment of endothelial barrieropen-angle glaucomaocular hypertensionglaucomaneurodegenerative disease
✦AI Summary

ROCK2 is a serine/threonine protein kinase that serves as a critical regulator of actin cytoskeleton dynamics and cell contractility through phosphorylation of multiple effector proteins including MYL9 and other cytoskeletal regulators. The kinase controls diverse cellular processes including stress fiber formation, focal adhesion assembly, and cell migration 1. Beyond cytoskeletal regulation, ROCK2 modulates immune homeostasis by regulating the balance between pro-inflammatory Th17 cells and anti-inflammatory regulatory T cells via STAT3/STAT5 signaling 2, and functions as a negative regulator of angiogenesis 3. ROCK2 plays pathological roles in multiple diseases: chr2 graft-versus-host disease (cGVHD), where selective ROCK2 inhibition with belumosudil achieves 74-77% overall response rates with durable remissions 24; liver fibrosis, where endothelial and perivascular ROCK2 upregulation promotes pro-fibrotic signaling 3; skin fibrosis, where ROCK2 operates downstream of the mechanotransducer TAGLN to regulate glucose metabolism and fibroblast contractility 1; and allergic asthma, where SUMOylation-mediated ROCK2 activation drives goblet cell metaplasia 5. Additionally, ROCK2-mediated pericyte contractility impairs tumor vasculature function 6, and ROCK2 regulates epithelial barrier integrity through claudin-1 expression 7 and inflammatory responses in epidermis via adherens junction disruption 8. These findings establish ROCK2 as a therapeutically targetable kinase across fibrotic, inflammatory, and immune disorders.

Sources cited
1
Belumosudil, a ROCK2 inhibitor, reduces Th17 cells and enhances regulatory T cells; achieves 74-77% overall response rate in chronic graft-versus-host disease
PMID: 34265047
2
ROCK2 upregulation in liver endothelial cells and perivascular hepatic stellate cells drives pro-fibrotic signaling and liver fibrosis
PMID: 41794026
3
ROCK2 regulates skin fibrosis through the TAGLN-RhoA/ROCK2-SLC2A3 mechano-metabolic axis controlling fibroblast contractility and glycolysis
PMID: 39781462
4
Belumosudil ROCK2 inhibition produces 65-69% overall response rate with durable responses and corticosteroid reductions in treatment-refractory chronic graft-versus-host disease
PMID: 33877856
5
ROCK2-mediated pericyte contractility contributes to tumor vasculature dysfunction and poor outcomes
PMID: 34650057
6
ROCK2 regulates epithelial barrier function and inflammatory response in epidermis independently from myosin II activation via cytoskeletal and transcriptional mechanisms
PMID: 36890793
7
ROCK1/2 pathway mediates Piezo1 regulation of claudin-1 tight junction protein expression and intestinal epithelial barrier function
PMID: 33636174
8
SUMOylation on K1007 activates ROCK2 to promote goblet cell metaplasia and mucus hypersecretion in allergic asthma
PMID: 37393345
Disease Associationsⓘ20
open-angle glaucomaOpen Targets
0.58Moderate
ocular hypertensionOpen Targets
0.58Moderate
glaucomaOpen Targets
0.55Moderate
neurodegenerative diseaseOpen Targets
0.55Moderate
graft versus host diseaseOpen Targets
0.50Moderate
cardiovascular diseaseOpen Targets
0.38Weak
immune system diseaseOpen Targets
0.38Weak
Fuchs endothelial corneal dystrophyOpen Targets
0.36Weak
basal cell carcinomaOpen Targets
0.32Weak
Fuchs' endothelial dystrophyOpen Targets
0.31Weak
chronic graft versus host diseaseOpen Targets
0.30Weak
uterine fibroidOpen Targets
0.29Weak
corneal edemaOpen Targets
0.28Weak
sialadenitisOpen Targets
0.21Weak
heart diseaseOpen Targets
0.21Weak
retinopathy of prematurityOpen Targets
0.20Weak
Non-immune hydrops fetalisOpen Targets
0.15Weak
hepatocellular carcinomaOpen Targets
0.11Weak
DextrocardiaOpen Targets
0.11Weak
amyotrophic lateral sclerosisOpen Targets
0.10Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets13
AMA0076Phase II
Rho-associated protein kinase inhibitor
glaucoma
AT-13148Phase I
MAP kinase-activated protein kinase 2 inhibitor
BELUMOSUDILApproved
Rho-associated protein kinase 2 inhibitor
graft versus host disease
BELUMOSUDIL MESYLATEApproved
Rho-associated protein kinase inhibitor
graft versus host disease
DE-104Phase II
Rho-associated protein kinase inhibitor
ocular hypertension
FASUDILApproved
Rho-associated protein kinase inhibitor
cardiovascular disease
NETARSUDILApproved
Rho-associated protein kinase inhibitor
open-angle glaucoma
NETARSUDIL DIMESYLATEApproved
Rho-associated protein kinase inhibitor
open-angle glaucoma
RIPASUDILApproved
Rho-associated protein kinase inhibitor
glaucoma
RIPASUDIL HYDROCHLORIDE DIHYDRATEApproved
Rho-associated protein kinase inhibitor
glaucoma
SAR-407899Phase II
Rho-associated protein kinase inhibitor
diabetic nephropathy
VEROSUDILPhase II
Rho-associated protein kinase inhibitor
Y-39983Phase I/II
Rho-associated protein kinase inhibitor
Related Genes
MAPK3Protein interaction99%KRIT1Protein interaction98%MYL2Protein interaction98%MYL11Protein interaction98%MYL5Protein interaction95%PIP5K1CProtein interaction94%
Tissue Expression6 tissues
Lung
100%
Heart
97%
Brain
75%
Ovary
59%
Liver
50%
Bone Marrow
37%
Gene Interaction Network
Click a node to explore
ROCK2MAPK3KRIT1MYL2MYL11MYL5PIP5K1C
PROTEIN STRUCTURE
Preparing viewer…
PDB8X92 · 2.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.35Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.25 [0.18–0.35]
RankingsWhere ROCK2 stands among ~20K protein-coding genes
  • #1,119of 20,598
    Most Researched308 · top 10%
  • #210of 1,025
    FDA-Approved Drug Targets7 · top quartile
  • #1,506of 17,882
    Most Constrained (LOEUF)0.35 · top 10%
Genes detectedROCK2
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study.
PMID: 34265047
Blood · 2021
1.00
2
Selective targeting of endothelial and perivascular angiocrine ROCK2 treats liver fibrosis.
PMID: 41794026
Cell · 2026
0.90
3
TAGLN-RhoA/ROCK2-SLC2A3-mediated Mechano-metabolic Axis Promotes Skin Fibrosis.
PMID: 39781462
Int J Biol Sci · 2025
0.80
4
ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease.
PMID: 33877856
J Clin Oncol · 2021
0.70
5
Targeting the ROCK2/UBA52/DRP1 axis enhances ferroptosis and overcomes pemigatinib resistance in Cholangiocarcinoma.
PMID: 40615369
Cell Death Dis · 2025
0.68