Our key findings are: (i) loss of CRB2 from rod photoreceptors results in retinitis pigmentosa, mainly at the peripheral and central superior retina; (ii) CRB2 in rod photoreceptor cells is required to maintain the rod photoreceptor layer and retinal electrical responses; (iii) loss of CRB2 in rods and concomitant loss of CRB1 leads to an exacerbation of the retinitis pigmentosa phenotype; (iv) ablation of CRB2 from rods with concomitant loss of CRB1 results in visual function impairment. Here, CRB2 is linked to retinitis pigmentosa.