Figure 2.

Molecular mechanisms of STGD1 (ABCA4-retinopathy) a schematic of ABCA4 protein structure (A), the visual cycle (B), transport (C) and failure of transport leading to retinal degeneration (D). The ABCA4 gene transcribes a large retina-specific ABCA4 protein with two transmembrane domains (TMD), two glycosylated extracellular domains (ECD) and two nucleotide-binding domains (NBD) (A). All-trans retinal is released from the light-activated rhodopsin/cone opsin into the rod/cone outer segments (B) to form a complex with phosphatidylethanolamine (PE), resulting in N-ret-PE, then this complex is actively transported to the disc surface by ABCA4 (C). Failure of this transport results in accelerated deposition of a major lipofuscin fluorophore (A2E) in the RPE, which causes RPE dysfunction and cell death, with subsequent photoreceptor cell loss over time (D).