LCA5 (lebercilin) is a ciliary protein essential for intraflagellar transport (IFT) in photoreceptor cilia, playing a critical role in the ciliary transport of outer segment proteins 1. Biallelic LCA5 mutations cause one of the most severe forms of Leber congenital amaurosis (LCA), characterized by early-onset, rapid photoreceptor degeneration and severe visual impairment 23. Mechanistically, lebercilin localizes at the bulge region of the photoreceptor outer segment alongside RP1 and IFT proteins (IFT81, IFT88), where it is crucial for membrane disc formation 4. Loss of LCA5 function causes abnormal localization and accumulation of ciliary proteins like CEP290 and IFT88 along the axoneme, leading to rhodopsin mislocalization, shortened outer segments, and photoreceptor cell death 23. Clinically, LCA5-associated disease presents with nystagmus, night blindness, and progressive visual loss leading to blindness by the third decade of life 5. Gene augmentation therapy with AAV8-hLCA5 shows promise when delivered early (before postnatal day 30 in murine models), achieving structural and functional photoreceptor rescue 64. Small molecule treatments (eupatilin, fasudil) show therapeutic potential in reducing ciliary protein accumulation and improving rhodopsin trafficking 2. LCA5 mutations account for approximately 7.6% of LCA cases in some populations, though frequency varies by cohort 57.