Non-syndromic Retinitis Pigmentosa (NsRP) was well known as one of the causes of visual impairment already in the 19th century. Giuseppe Albertotti, Professor of Ophthalmology at the University of Modena (Italy) in 1893, described a high prevalence of NsRP in a geographic isolate, the small village of Colloro, in northwestern Italy. In two living descendants, similarly affected with NsRP, we identified pathogenic variants in the CRB1 gene as the cause of the visual impairment. Reconstruction of an extended pedigree demonstrated that all affected subjects go back to a single couple married in Colloro in the early 17th century and confirmed an autosomal recessive pattern of inheritance of the disease in this population. We also provide structural data on the novel CRB1 pathogenic variant. CRB1, is a transmembrane protein primarily expressed in the retina, which plays a pivotal role in photoreceptor survival and maintaining retinal architecture. Pathogenic variants in the CRB1 gene are associated with retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), highlighting its significance in retinal health as these pathogenic variants lead to photoreceptor degeneration and progressive vision loss.