Expression of the retina-specific flippase, ABCA4, in epidermal keratinocytes

ATP-binding cassette, sub-family A, member 4 (ABCA4) is a photoreceptor transmembrane protein that is responsible for flipping N-retinylidene-phosphatidylethanolamine, a key intermediate in the visual cycle, from the lumen to the cytoplasmic leaflet of photoreceptor outer segment disks. Mutations in ABCA4 cause a build-up of toxic retinoids resulting in a variety of retinal degenerative phenotypes, including Stargardt disease, cone-rod dystrophy and retinitis pigmentosa. Since many of the ABCA4 variants are rare and non-exomic, their pathogenicity is often difficult to demonstrate statistically. Given that the neural retina is inaccessible to molecular analysis in living patients, we use patient-specific induced pluripotent stem cell (iPSC)-derived retinal neurons to identify and model disease-causing mutations. Here we demonstrate that a truncated version of the retinal-specific transmembrane enzyme ABCA4 is expressed in epidermal keratinocytes and is required for cellular proliferation and viability at late passage. This finding is of great importance for labs that wish to investigate the pathophysiology of novel ABCA4 -variants, without having to incur the added expense and scientific expertise associated with iPSC generation, culture and differentiation. Likewise, this finding is also important for those intending to generate iPSCs from patient specific keratinocytes, which can prove difficult when ABCA4 mutations are present.