This study investigates the central projections of melanopsin-expressing retinal ganglion cells (mRGCs) in mice. By using a tau-lacZ knock-in mouse model, the authors visualized the axons of mRGCs that normally express melanopsin. The projections were found to be more widespread than previously recognized, targeting several regions in the hypothalamus, amygdala, lateral geniculate complex, superior colliculus, and periaqueductal gray. The projections to the suprachiasmatic nucleus (SCN) and intergeniculate leaflet (IGL) were particularly dense, with a strong bilateral symmetry in the SCN. Monocular enucleation experiments revealed that the projections from mRGCs to these targets are predominantly crossed, except for the SCN. Double-immunofluorescence experiments showed that while mRGCs provide most of the retinal input to the SCN, IGL, and lateral habenula, other retinal ganglion cells also contribute to these targets. The study provides a comprehensive overview of the central projections of mRGCs and highlights their diverse roles in various brain regions.This study investigates the central projections of melanopsin-expressing retinal ganglion cells (mRGCs) in mice. By using a tau-lacZ knock-in mouse model, the authors visualized the axons of mRGCs that normally express melanopsin. The projections were found to be more widespread than previously recognized, targeting several regions in the hypothalamus, amygdala, lateral geniculate complex, superior colliculus, and periaqueductal gray. The projections to the suprachiasmatic nucleus (SCN) and intergeniculate leaflet (IGL) were particularly dense, with a strong bilateral symmetry in the SCN. Monocular enucleation experiments revealed that the projections from mRGCs to these targets are predominantly crossed, except for the SCN. Double-immunofluorescence experiments showed that while mRGCs provide most of the retinal input to the SCN, IGL, and lateral habenula, other retinal ganglion cells also contribute to these targets. The study provides a comprehensive overview of the central projections of mRGCs and highlights their diverse roles in various brain regions.