Inherited retinal diseases (IRD) are a major cause of early-onset blindness worldwide. The underlying molecular defects have been found in ~65% of individuals with IRD, mostly coding mutations. Due to the rapidly expanding whole genome sequencing, the number of non-coding mutations is emerging. The paradigm of non-coding variation in IRD is strengthened by a subset of autosomal recessive (AR) monogenic IRD in which only a single mutation can be found in the coding region of the expected disease-causing gene. One of the most striking examples is AR Stargardt disease (STGD1), the most frequent IRD, affecting ~1/8.000 persons and caused by biallelic mutations in ABCA4. In 20-35% of STGD1 however, no or only one coding variant can be identified. This renders STGD1 an excellent model disease for non-coding variation. The general aim of this project is to provide insight into the cis-regulation of ABCA4 in the retina, which is still unknown. We will decipher the cis-regulatory landscape of the ABCA4 region in human retina. Enhancer activity of identified retinal cis-regulatory elements (CREs) will be assessed by massively parallel reporter assays in mouse retinal explants. Genomic profiling of the ABCA4 locus will be conducted in IRD patients with a single coding ABCA4 mutation. Functional characterization of retinal CREs of the ABCA4 region will contribute to understanding the regulation of ABCA4 and to the role of CREs in the molecular pathogenesis of STGD1 when disrupted.