CRB1 encodes a cell polarity complex component essential for retinal photoreceptor morphogenesis and epithelial cell organization. The protein maintains cell polarization and adhesion through its role in establishing apical/basal polarity and functions within apical junction complexes 1. CRB1 mediates heterophilic cell-cell adhesion and contributes to protein-containing complexes at the plasma membrane and apical plasma membrane 1. CRB1 mutations cause three distinct inherited retinal dystrophies: Leber congenital amaurosis (LCA), the most severe form presenting with visual impairment within the first months of life; retinitis pigmentosa (RP), characterized by early-onset progressive vision loss before adolescence; and pigmented paravenous chorioretinal atrophy 12. In a large Italian IRD cohort, CRB1 mutations accounted for 2.7% of solved cases, with CRB1 being the second most frequent gene in EOSRD patients (10.5%) in a Chinese cohort 34. Disease exhibits phenotypic heterogeneity with variable retinal structural alterations and functional outcomes 5. Currently, no approved gene therapy exists for CRB1 retinopathies, though research using animal models and human-derived systems including hiPSC-derived retinal organoids is advancing potential augmentation therapeutic approaches 2. Understanding CRB1 dysfunction mechanisms remains critical for developing predictive molecular diagnostics and therapeutic interventions.