Autophagy and exosome biogenesis are closely linked, with secretory autophagy playing a key role in the release of proteins and exosomes. Exosomes, initially considered waste products, are now recognized as important intercellular messengers with therapeutic and diagnostic potential. Secretory autophagy allows the release of proteins that bypass the conventional secretory pathway, such as IL-1β and IL-18, and is involved in the formation of amphisomes, which integrate autophagic and endosomal pathways. Regulatory proteins like mTORC1 are potential therapeutic targets for modulating cellular secretion. Exosome biogenesis involves the formation of multivesicular bodies (MVBs) through endocytosis, which then fuse with the plasma membrane to release exosomes. The ESCRT machinery and SNARE proteins are involved in exosome formation and autophagy. Exosomes can modulate autophagy by delivering microRNAs, autophagic proteins, and TLR ligands, influencing processes such as mitochondrial turnover and immune responses. Autophagy also affects exosome maturation and release, with mTORC1 inhibition enhancing exosome secretion. Amphisomes, formed by the fusion of autophagosomes and MVBs, play a role in both autophagy and exosome release, and are involved in various cellular processes, including viral replication, parasite degradation, and neurodegenerative diseases. The regulation of amphisomes is crucial for maintaining cellular homeostasis and is implicated in conditions such as cataracts and age-related oocyte dysfunction. Overall, the interplay between autophagy and exosome biogenesis is a complex and dynamic process with significant implications for cellular function and disease.Autophagy and exosome biogenesis are closely linked, with secretory autophagy playing a key role in the release of proteins and exosomes. Exosomes, initially considered waste products, are now recognized as important intercellular messengers with therapeutic and diagnostic potential. Secretory autophagy allows the release of proteins that bypass the conventional secretory pathway, such as IL-1β and IL-18, and is involved in the formation of amphisomes, which integrate autophagic and endosomal pathways. Regulatory proteins like mTORC1 are potential therapeutic targets for modulating cellular secretion. Exosome biogenesis involves the formation of multivesicular bodies (MVBs) through endocytosis, which then fuse with the plasma membrane to release exosomes. The ESCRT machinery and SNARE proteins are involved in exosome formation and autophagy. Exosomes can modulate autophagy by delivering microRNAs, autophagic proteins, and TLR ligands, influencing processes such as mitochondrial turnover and immune responses. Autophagy also affects exosome maturation and release, with mTORC1 inhibition enhancing exosome secretion. Amphisomes, formed by the fusion of autophagosomes and MVBs, play a role in both autophagy and exosome release, and are involved in various cellular processes, including viral replication, parasite degradation, and neurodegenerative diseases. The regulation of amphisomes is crucial for maintaining cellular homeostasis and is implicated in conditions such as cataracts and age-related oocyte dysfunction. Overall, the interplay between autophagy and exosome biogenesis is a complex and dynamic process with significant implications for cellular function and disease.