DAPL1 protein prevents PANoptosis—a catastrophic form of cell death combining apoptosis, necroptosis, and pyroptosis—in retinal pigment epithelium cells during experimental age-related macular degeneration. The mechanism involves DAPL1's inhibition of GRP75, a chaperone protein that facilitates dangerous connections between mitochondria and endoplasmic reticulum membranes. This research represents a significant advance in AMD pathophysiology, potentially identifying the first targetable molecular brake on retinal degeneration. Previous AMD research focused primarily on inflammation and oxidative stress, but this work reveals how cellular organelles communicate during disease progression. The discovery is particularly valuable because AMD affects over 200 million people globally with no curative treatments available. However, the findings come from experimental models rather than human studies, and translating organelle-level interventions into viable therapies remains challenging. The DAPL1-GRP75 axis could represent a new therapeutic paradigm, shifting focus from managing AMD symptoms to preventing the fundamental cellular collapse that drives vision loss. This mechanistic insight may also apply to other neurodegenerative diseases where similar organelle dysfunction occurs.