ABCA4, a member of the ATP-binding cassette (ABC) transporter superfamily, is preferentially located along the rim region of rod and cone photoreceptor outer segment disc membranes. It uses ATP-binding and hydrolysis energy to transport N-retinylidene-phosphatidylethanolamine from the lumen to the cytoplasmic leaflet of disc membranes. This function is crucial for clearing all-trans-retinal and excess 11-cis-retinal from photoreceptor cells, preventing the accumulation of toxic retinoid compounds, and thus playing a vital role in the visual cycle [2].

Loss-of-function mutations in ABCA4 cause autosomal recessive Stargardt macular degeneration (STGD1) and related retinopathies. These diseases show a wide clinical spectrum, ranging from early-onset and fast-progressing cone-rod dystrophy and retinitis pigmentosa-like phenotypes to very late-onset cases sometimes resembling age-related macular degeneration. Over 1200 disease-causing mutations of various types have been identified in ABCA4 [1]. Different combinations of ABCA4 variants can lead to different disease phenotypes. For example, the hypomorphic variant c.5603A>T (p.Asn1868Ile) is associated with late-onset disease and can account for a significant fraction of ABCA4-related diseases, especially in monoallelic cases, and helps distinguish ABCA4 disease from age-related macular degeneration [3].

In conclusion, ABCA4 is essential for maintaining normal visual function by regulating the visual cycle. Studies on ABCA4-related diseases, especially those based on genetic mutations, have expanded our understanding of the complexity of Mendelian diseases. The identification of numerous disease-causing mutations and their associated phenotypes in ABCA4 has provided a foundation for developing therapeutic approaches for ABCA4-associated retinopathies [1,2].