Gene therapy has become a promising treatment for inherited retinal dystrophies (IRDs), but understanding the genetic mechanisms involved is essential for its success. Various approaches, such as gene augmentation and DNA/RNA-based therapies, have shown effectiveness in some clinical trials. However, gene augmentation is not effective for some dominant mutations and genome editing produces off-target effects. Here, we review safer and viable alternatives that are being evaluated in preclinical models and clinical trials to address this challenge. We propose a novel perspective based on protein-targeting therapies, which although promising, remain unexplored. We suggest that frameshift variants, which produce novel epitopes, may allow for the development of mutant protein targeting agents for selective protein degradation. This approach could be useful for dominant variants, where gene replacement is ineffective. By examining these approaches, we aim to guide more targeted and effective gene therapies for IRDs, offering potential treatments where current methods fall short.