Protein / target
Caspase-1
Protein at a glance
Biological role
Cysteine-type endopeptidase activity
Primary system
Immune system
Strongest disease association
Abnormality of the genital system
Therapeutic maturity
Clinical-stage target
Druggability
Small molecule
Clinical development
3 in clinical development
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides (PubMed:15326478, PubMed:15498465, PubMed:1574116, PubMed:26375003, PubMed:32051255, PubMed:37993714, PubMed:7876192, PubMed:9334240). Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a pro-inflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes (PubMed:15326478, PubMed:15498465, PubMed:1574116, PubMed:32051255, PubMed:7876192). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:15498465, PubMed:1574116, PubMed:7876192). Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:26375003). In contrast to cleavage of interleukin IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32051255, PubMed:32109412, PubMed:32553275). Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (PubMed:22464733). Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive (PubMed:28314590). In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly (PubMed:20197547)
Subcellular location
Domains and Gene Ontology detail (44)Hide
Domains & features
Gene Ontology
- CAIM2 inflammasome complex
- Ccytoplasm
- Ccytosol
- CIPAF inflammasome complex
- Cmicrotubule
- CNLRP1 inflammasome complex
- CNLRP3 inflammasome complex
- Cnucleolus
- Cplasma membrane
- Cprotease inhibitor complex
- Cprotein-containing complex
- FCARD domain binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Immune signalling
- ·Thiol protease involved in a variety of inflammatory processes by proteolytically cleavi…
- ·cytokine binding
- ·cytokine precursor processing
- ·positive regulation of inflammatory response
Proteolysis
- ·Thiol protease involved in a variety of inflammatory processes by proteolytically cleavi…
- ·protease inhibitor complex
- ·cysteine-type endopeptidase activity
- ·endopeptidase activity
Apoptosis & cell death
- ·cysteine-type endopeptidase activator activity involved in apoptotic process
- ·apoptotic process
- ·positive regulation of apoptotic process
- ·TP53 Regulates Transcription of Caspase Activators and Caspases
Transcriptional regulation
- ·TP53 Regulates Transcription of Caspase Activators and Caspases
View underlying pathways (11)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Caspase-1 inhibitor
Appears in clinical studies involving epilepsy, psoriasis vulgaris, focal epilepsy, COVID-19
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,127 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 3 total
epilepsy · psoriasis vulgaris · focal epilepsy
Hepatic fibrosis · cirrhosis of liver · hepatitis C virus infection
fibrosis · metabolic dysfunction-associated steatohepatitis · hepatitis C virus infection
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
ClinicalTrials.gov via the drug-target graph.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationPharmacological Inhibitors of the NLRP3 Inflammasome.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.