Abstract: Vision loss from ocular diseases affects millions worldwide and represents a significant challenge to global health. One of these conditions, retinitis pigmentosa (RP), comprises a heterogeneous group of inherited retinal disorders caused by mutations in a wide array of genes. Although substantial progress has been made in elucidating the molecular causes of RP and related inherited retinal diseases, effective therapies remain limited, particularly for monogenic inherited forms (Tsang and Sharma, 2018). The clinical development of several adeno-associated virus (AAV)-based gene augmentation therapies is advancing; some have gained regulatory approval, including Luxturna for RPE65-associated retinal dystrophy (Ng et al., 2024). The eye presents several advantages as a target organ for gene therapy; it is immuneprivileged, anatomically accessible, and amenable to longitudinal monitoring through imaging and functional testing (Ng et al., 2024). These features position the eye as a model system for implementing novel genetic therapies, including gene editing and transcriptional modulation. However, current gene augmentation may be limited by the lack of regulatory elements. To broaden therapeutic strategies beyond traditional gene augmentation, especially for conditions driven by gene loss-of-function or haploinsufficiency, innovative approaches such as endogenous gene activation are urgently needed.