Aryl hydrocarbon receptor interacting protein-like 1 (AIPL1) is a photoreceptor-specific molecular co-chaperone. It functions by interacting with molecular chaperones HSP90 and HSP70 to facilitate the correct folding and assembly of the retinal cGMP phosphodiesterase (PDE6) holoenzyme, which is crucial for the phototransduction cascade [2]. Mutations in AIPL1 are mainly associated with autosomal recessive Leber congenital amaurosis (LCA), a severe early-onset inherited retinopathy [2].

Mouse models have revealed the importance of AIPL1 in the stability and function of heteromeric phosphodiesterase 6 (PDE6) [1]. In zebrafish, the cone-specific aipl1b gene is required for cone survival, and Aipl1 is necessary for the stability of Pde6c and Gc3, key components in cGMP metabolism in photoreceptors [4]. A Nuclease technology-generated AIPL1 knockout in human induced pluripotent stem cell-derived retinal organoids recapitulated molecular features of LCA4, showing decreased rod-specific PDE6α and β and increased cGMP levels [3].

In conclusion, AIPL1 is essential for photoreceptor function, particularly in the folding and assembly of PDE6. Studies using gene knockout models in mice, zebrafish, and human retinal organoids have enhanced our understanding of its role in maintaining photoreceptor integrity and function, and its association with Leber congenital amaurosis.