Objective
Many severe genetic and age-related diseases are driven by the accumulation of misfolded proteins within the endoplasmic reticulum, leading to chronic cellular stress, tissue damage and organ failure. Despite major advances in targeted protein degradation, no current technology can selectively eliminate toxic proteins residing inside this cellular compartment. As a result, patients affected by the so-called ER-storage diseases (e.g. collagenopathies, corneal dystrophies or serpinopathies) still lack therapies that address the root cause of their condition.
Building on discoveries from the ERC AUTO-SELECT project, this Proof of Concept aims to translate the identification of ER-phagy as a selective, mutation-agnostic ER quality-control pathway into a therapeutic strategy. The project will develop and validate small molecules selectively activating ER-phagy and promoting the removal of disease-causing proteins without inducing global autophagy. This represents a first-in-class approach to degrade toxic ER-resident proteins that are inaccessible to existing modalities.
The PoC will confirm mechanism of action, demonstrate clearance of pathogenic proteins in validated disease models, and assess selectivity and cellular safety. In parallel, intellectual property will be consolidated within a dedicated spin-out, Eracle Bio, and aligned with a structured partnering and licensing strategy supported by an experienced life sciences investor. By delivering validated lead compounds and a partnering-ready data package, the project creates a clear pathway from ERC-funded discovery to industrial collaboration and clinical translation.
If successful, this work will establish a new therapeutic paradigm focused on compartment-specific protein degradation and open scalable opportunities for treating multiple currently untreatable diseases, with significant impact for both science and society.
Fields of science (EuroSciVoc)
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2026-POC
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
00185 ROMA
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.