In the vertebrate retina, rod and cone photoreceptor cells contain functionally specialised and morphologically distinct outer segment (OS) compartments comprising membrane discs, which house the light-absorbing photopigments. Mutations affecting the outer segment include prominin-1 (prom1) and photoreceptor cadherin (cdhr1), which are associated with inherited retinal degenerative disorders. However, the role of these genes in OS morphogenesis remained largely unclear. To address this question, Brittany Carr and colleagues (Carr et al., 2021) characterise Xenopus prom1- and cdhr1-null mutants generated by CRISPR-Cas9. Loss of prom1 leads to disrupted photoreceptor morphology, such as convoluted overgrown membranes, indicating a role in regulating OS membrane disc size. Cone outer segments are more severely affected than rods and show impaired electrical signals in electroretinograms. cdhr1 mutant phenotypes were more subtle, but electron microscopy analysis revealed defects in OS disc orientation and growth. The authors conclude that the two genes have distinct functions and rule out previously proposed roles in OS disc membrane evagination and disc fusion. Interestingly, in the OS of prom1-null animals the authors observe an increase in Hoechst-stained autofluorescent deposits, suggesting that secondary toxic effects caused by the mutation might drive retinal degeneration. Collectively, this work reveals important roles for Prom1 and Cdhr1 in the higher-order organisation of the outer segment, and may inform efforts to develop retinal degeneration therapies.