Hereditary retinal disease (IRD) is a leading cause of early-onset blindness affecting 350,000 people in Europe. Significant progress has been made in the genomic underpinnings of IRD, leading to new therapies entering the clinic. Despite these advances, there are significant gaps in knowledge that impede molecular diagnosis in more than half the cases. We and others have provided a proof-of-concept for an emerging role of noncoding DNA variation in unresolved IRD, affecting splicing or regulation. Here we pursue a methodological and conceptual shift from classical coding to noncoding genomics. Our main goal is to create a framework to resolve missing heritability in IRD using integrated omics and gene editing in human cellular and animal models. Specifically, we will perform reverse phenotyping and generate cellular models of undiagnosed monoallelic patients with suspected recessive IRD. We will establish an integrative omics framework to accelerate diagnosis in unresolved IRD. Furthermore, we will decipher the regulation of IRD genes in the human retina. Integration of omics datasets will improve genome annotation in human retina. We will unravel novel regulatory mechanisms underlying dominant IRD in human cellular and CRISPR/Cas9-generated animal models. Finally, we will transfer research findings to the clinic through ERN-EYE and patient advocacy organizations. Our complementary expertise, track record and pan-European network provide a unique opportunity to address the unmet need of missing heritability in IRD, paving the way for precision medicine in IRD.