Autophagy is a conserved cellular process in eukaryotes, including mammals, that degrades long-lived proteins and damaged organelles via autophagosomes, which fuse with lysosomes for degradation. The core molecular machinery of mammalian autophagy includes the ULK1/ULK2 complex, Atg12-Atg5 conjugation system, Atg8/LC3 lipidation system, and class III PtdIns3K complex. These components work together to initiate and regulate autophagy. Signaling pathways, such as the mTORC1 pathway, control autophagy in response to nutrient and energy status, while AMPK and p53 also play regulatory roles. The Bcl-2 family of proteins modulates autophagy by interacting with Beclin 1 and the PtdIns3K complex. Autophagy is essential for cellular homeostasis and survival under stress, but dysregulated autophagy can lead to disease. Recent advances have improved understanding of the molecular mechanisms and signaling pathways involved in mammalian autophagy, highlighting its importance in health and disease.Autophagy is a conserved cellular process in eukaryotes, including mammals, that degrades long-lived proteins and damaged organelles via autophagosomes, which fuse with lysosomes for degradation. The core molecular machinery of mammalian autophagy includes the ULK1/ULK2 complex, Atg12-Atg5 conjugation system, Atg8/LC3 lipidation system, and class III PtdIns3K complex. These components work together to initiate and regulate autophagy. Signaling pathways, such as the mTORC1 pathway, control autophagy in response to nutrient and energy status, while AMPK and p53 also play regulatory roles. The Bcl-2 family of proteins modulates autophagy by interacting with Beclin 1 and the PtdIns3K complex. Autophagy is essential for cellular homeostasis and survival under stress, but dysregulated autophagy can lead to disease. Recent advances have improved understanding of the molecular mechanisms and signaling pathways involved in mammalian autophagy, highlighting its importance in health and disease.