CACNA1F encodes a voltage-dependent L-type calcium channel that activates at more hyperpolarized voltages and exhibits calcium-dependent inactivation. The channel mediates calcium ion import across the plasma membrane and is critical for retinal function, particularly in visual signal transduction 1. Mechanistically, CACNA1F variants disrupt normal calcium channel kinetics through multiple mechanisms. Loss-of-function mutations cause splicing defects and frameshifts leading to truncated proteins 2, while both gain- and loss-of-function variants can alter channel activation and inactivation kinetics 3. The location of mutations within the protein influences clinical severity, with N-terminal mutations producing more severe phenotypes 4. CACNA1F mutations cause X-linked retinal dystrophies, most notably incomplete congenital stationary night blindness (CSNB2) and Åland island eye disease (AIED) 14. CACNA1F variants account for approximately 3% of inherited retinal dystrophy cases 5. Additionally, CACNA1F mutations contribute to intellectual disability and global developmental delay in rare cases, with loss-of-function variants typically producing less severe phenotypes than gain-of-function variants 3. Genetic testing is essential for confirming CACNA1F-related diagnoses and enabling future gene-based therapeutic strategies, particularly as gene replacement approaches show promise for loss-of-function variants 15.