This review synthesizes mechanistic and transcriptomic insights that position PROM1 as a central regulator of photoreceptor and RPE integrity, reframing <i>Prom1</i> disease as a multi-compartment retinal disorder relevant to both inherited retinal dystrophies (IRDs) and atrophic age-related macular degeneration (aAMD). Here, PROM1 is linked to inherited retinal dystrophy.