Given the abundance of C16:0 ceramide in the normal retina and the severe C16:0 reduction owing to TLCD3B loss of function in Tlcd3b−/− mice, C16:0 ceramide might be the leading player causing retinal degeneration, and a higher compensation by C18:0 and C20:0 ceramides does not rescue retinal degeneration as effectively as C16:0 ceramide restoration. The gene discussed is TLCD3B; the disease is retinal degeneration.