PURPOSE: This minireview discusses desmosome and hemidesmosome disassembly and/or internalization and subsequent release METHODS: Literature review and discussion of novel findings relevant to the focus of the review. RESULTS: The RPE forms the outer blood-retinal barrier, and like other epithelia it has several different types of cell-cell junctions, such as desmosomes. The RPE provides key metabolic and nutrient support to photoreceptors and the function of normal vision. The RPE is a principal location of disease-associated changes in AMD, due to its essential role in visual homeostasis. Exosomes are lipid bilayer membrane vesicles of nanometer sizes that are released CONCLUSIONS: This review provides an overview of the current knowledge about desmosome and hemidesmosome disassembly in RPE, its intersection with the exosome pathway, and potential role in epithelial-mesenchymal transition. We discuss several potential targets for therapeutic intervention in pre-symptomatic or early-stage AMD in these pathways.