ABCA4 and severe early-childhood-onset retinal dystrophy: The pathophysiology of STGD is a result of defective ABCA4 transport of retinoids (as part of the visual cycle), resulting in an abnormal accumulation of lipofuscin and related toxic by-products (including A2E) in the RPE and photoreceptors, with subsequent cell dysfunction and death overtime.33 The abca4−/− knockout mouse model has been critical in elucidating this sequence of events and has also served as a model to test therapeutic approaches (see further).34