Investigations of retinal dystrophy (RD) mechanisms are rarely conducted in the context of mutations found in patients. Additionally, many RD-associated mutations are classified as ‘Variants of Uncertain Significance’, or VUS, and there is an urgent clinical need to develop methods that can lead to their reclassification as pathogenic or benign. Furthermore, therapies are completely lacking for most forms of RD. To address these shortfalls, RDCilia examines RD in the ciliopathy Bardet-Biedl syndrome (BBS), the second most common syndromic form of retinal disease, typically manifesting as rod-cone dystrophy. Like all ciliopathies, BBS is caused by defects in primary cilia, which are critical sensory and signaling organelles on most cell surfaces. In photoreceptors, the light sensing outer segment is a modified cilium. Focussing on the BBS2/RP74 ciliopathy gene associated with retinitis pigmentosa, RDCilia will use leading invertebrate (C. elegans) and vertebrate (zebrafish) animal models, as well as mammalian cells, together with knock-in gene editing technology and semi-high throughput whole animal small molecule screening, to achieve three primary objectives: (i) Interrogate RD mechanisms by modelling patient mutations in nematodes, (ii) inform RD molecular diagnosis by providing in vivo phenotypic evidence for VUS reclassification, and (iii) identify small molecules that reverse RD patient allele phenotypes in mammalian cells and animals. Altogether, RDCilia will couple basic biological insight to patient-centered disease mechanisms, provide a greater understanding of the genotype-phenotype conundrum in eye disorders, and determine routes to therapy.