The protein neural retina leucine zipper (Nrl) is a basic motif–leucine zipper transcription factor that is preferentially expressed in rod photoreceptors^,. It acts synergistically with Crx to regulate rhodopsin transcription^,,. Missense mutations in human NRL have been associated with autosomal dominant retinitis pigmentosa^,. Here we report that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones. The photoreceptors in the Nrl^−/− retina have cone-like nuclear morphology and short, sparse outer segments with abnormal disks. Analysis of retinal gene expression confirms the apparent functional transformation of rods into S cones in the Nrl^−/− retina. On the basis of these findings, we postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3.