The study investigates the role of melanopsin, an opsin-like protein, in the circadian clock and non-image-forming visual functions. Melanopsin is found in a subset of retinal ganglion cells (RGCs) that project to the suprachiasmatic nucleus (SCN), the brain's circadian pacemaker. The authors cloned the full-length cDNA for rat melanopsin and generated specific antibodies to label melanopsin-positive RGCs. Immunocytochemistry revealed that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of these RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, β-galactosidase-positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment and the pupillary light reflex. Intracellularly injected Lucifer Yellow (LY) was used to identify intrinsic light-sensitive RGCs, which were invariably melanopsin-positive. These findings suggest that melanopsin is the photopigment responsible for the intrinsic light sensitivity of these RGCs and their involvement in non-image-forming visual functions.The study investigates the role of melanopsin, an opsin-like protein, in the circadian clock and non-image-forming visual functions. Melanopsin is found in a subset of retinal ganglion cells (RGCs) that project to the suprachiasmatic nucleus (SCN), the brain's circadian pacemaker. The authors cloned the full-length cDNA for rat melanopsin and generated specific antibodies to label melanopsin-positive RGCs. Immunocytochemistry revealed that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of these RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, β-galactosidase-positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment and the pupillary light reflex. Intracellularly injected Lucifer Yellow (LY) was used to identify intrinsic light-sensitive RGCs, which were invariably melanopsin-positive. These findings suggest that melanopsin is the photopigment responsible for the intrinsic light sensitivity of these RGCs and their involvement in non-image-forming visual functions.