Autophagy is an intracellular degradation mechanism essential for cell homeostasis, differentiation and development. Autophagy has a major impact on various pathologies such as Alzheimer´s and aging. Our laboratories use different model systems to study the molecular basis and cellular mechanisms of rare diseases and their relationship with autophagy. These models include the yeast Saccharomyces cerevisiae, the social amoeba Dictyostelium discoideum, and mammalian cells in culture. Modeling rare disease in these simple organisms could open up new therapeutic possibilities.