Human opsin-2 is a G-protein coupled photoreceptor found in the disc membranes of rod outer segments (ROS) (Nathans & Hogness 1984). It is an integral membrane protein and covalently binds the chromophore 11-cis-retinal (11cRAL) to form rhodopsin (RHO). Binding occurs via a protonated Schiff base linkage at Lys-296 (Fan et al. 2002) with Glu-113 at helix 3 serving as the counterion of the protonated Schiff base (Han et al. 1993). The resultant 11-cis-retinyl (11c-retinyl) group attached to lysine is completely embedded within the RHO structure. Opsins found in cone outer segments which bind 11cRAL are described in the cone visual cycle. Unlike other GPCRs in which direct ligand binding activates the receptor, rhodopsin is in an inactive state when bound to 11c-retinyl (which acts as an inverse agonist).