*8.2. AIPL1*

Mutations in the gene encoding aryl hydrocarbon receptor-interacting protein-like 1 (*AIPL1*) causes LCA4 accounting for about 3% to 7% of autosomal recessive LCA [132,134,158–160]. The *AIPL1* gene encodes for a protein expressed in the photoreceptor and pineal gland [161]. In photoreceptors, AIPL1 is concentrated in the tip of the inner segmen<sup>t</sup> in proximity to the connecting cilia, acting as a co-chaperone involved in the folding, assembly and transport of the retinal cGMP phosphodiesterase (PDE6) heteromeric holoenzyme within photoreceptor outer segments [162–166].

One spontaneous occurring feline large animal model of LCA4 currently exists, the Persian cat [167]. This feline model, similar to human patients with LCA4, presents as an autosomal recessive severe retinal dystrophy. The disease is characterized by a very early photoreceptor loss, progressing to severe retinal degeneration before adulthood. This leads to very early blindness [167]. The feline phenotype is caused by a nonsense mutation at position c.577C>T producing a stop codon (p.Arg193Ter), leading to the production of a truncated non-functional protein [168]. The precise mechanisms of the severe phenotype in the feline model are ye<sup>t</sup> to be investigated. The feline model represents a valuable large animal model for mechanistic studies underlying *AIPL1*-LCA in humans.
