Cellular homeostasis is maintained by targeting cytosolic proteins to lysosomes for degradation through chaperone-mediated autophagy (CMA). CMA is activated in response to stress and is impaired with age. A recent study in mice has revealed that dietary lipids inhibit lysosomal uptake of proteins through lysosome-associated membrane glycoprotein 2A (LAMP2A), thereby limiting CMA. The lipid composition of lysosomal membranes was altered following a high-fat diet, resulting in the formation of lipid microdomains, where LAMP2A is proteolytically degraded. Interestingly, similar changes in the composition of lysosomal membranes were observed in ageing mice, indicating that a common mechanism underlies impaired CMA activity. The authors suggest that the emerging regulatory role of lipid metabolism in CMA could be targeted in ageing and age-related diseases.