Abstract Inherited retinal diseases (IRD) are a major cause of early-onset blindness, profoundly affecting millions of patients. Given the clinical and genetic heterogeneity of IRD, targeted gene therapy is emerging as the main effective approach for treating the disease with many clinical trials currently underway. To maximize the benefit of these emerging therapies to patients, molecular diagnosis is the first critical step. In coordinating with the ClinGen Ocular Clinical Domain Working Group committee, we propose to establish a new variant curation expert panel (VCEP) that will focus on developing disease and gene specifications and curating expert assessment of variants in the seven X-linked IRD genes, including RPGR, CHM, RS1, RP2, OFD1, NDP, and CACNA1F. Collectively, mutations in these genes account for 15% of IRD patients. We have identified a distinguished panel of scientists across the world who will commit to this effort with diverse expertise: practicing ophthalmologic physicians, clinical diagnostic laboratory directors, and world-leading researchers studying the function of the X-linked IRD genes in the clinical and research domains. These experts bring complementary knowledge and resources to this effort including functional laboratory assays to assess the impact of patient variants, clinical trials for gene-based treatments, and collections of patient samples with sequenced variants and a detailed clinical history. Together with dedicated bioinformatics, curatorial, and administrative support, the X-linked IRD Variant Curation Panel proposed will deploy the FDA approved ClinGen infrastructure tools and processes in combination with the supportive resources we propose to collect, organize and provide to the panel to develop rule specifications for X-linked IRD gene curation. With our panel and team of coordinated curation volunteers, we will curate and expertly assess the variants in these genes. The products of this effort will be two-fold. First, specifications that can be applied to assess new variants in the seven genes and can be adapted for other X-linked IRD genes. And second, curated variants in the seven X-linked IRD genes with three-star (expert panel assessed) ratings in the ClinVar databasethat will improve the assessment of de novo patient variants and enable treatments with gene-based therapies.