Selective autophagy is a more specific process than previously thought, with autophagic adapter proteins like p62 and NBR1 playing key roles. These proteins are selectively degraded by autophagy and act as cargo receptors for ubiquitinated substrates. They interact with the autophagosomal marker protein LC3 via a LIR motif, and their ability to polymerize and recognize substrates is essential for efficient selective autophagy. These features are conserved across species, including the yeast Cvt pathway and C. elegans P granules. Selective autophagy regulates cell signaling, affecting oxidative stress, tumorigenesis, and immunity. Autophagy is an evolutionarily conserved process that sequesters and transports organelles and macromolecules to lysosomes for degradation. It is involved in nutrient recycling during starvation and in the innate immune response against pathogens. Yeast genetics has been crucial in understanding autophagy machinery, with 34 ATG genes identified. Two ubiquitin-like conjugation systems are part of the conserved autophagic machinery, and four additional protein complexes are required for autophagy. In mammals, the ULK1 complex and class III PtdIns 3-kinase regulate autophagosome formation. ATG8 proteins, such as LC3 and GABARAP, are conjugated to phosphatidylethanolamine (PE) and serve as autophagic markers. Chaperone-mediated autophagy (CMA) degrades soluble proteins with a KFERQ motif. The Cvt pathway in yeast delivers lysosomal enzymes to the vacuole. Selective autophagy targets protein inclusions, organelles, and pathogens, including aggrephagy (degradation of protein aggregates), pexophagy (peroxisomes), mitophagy (mitochondria), xenophagy (bacteria/viruses), reticulophagy (surplus ER), and ribophagy (ribosomes). p62 and NBR1 are selective autophagy substrates and cargo receptors. p62 is a 440-amino acid protein with a PB1 domain, ZZ domain, LIR motif, and UBA domain. It binds to ubiquitin and is involved in autophagic degradation of protein aggregates, misfolded proteins, and damaged mitochondria. NBR1 is also a selective autophagy substrate and cargo receptor, with a similar domain structure to p62 but also containing a FW domain. The LIR motif is crucial for p62 and NBR1 interaction with LC3/GABARAP family proteins. The LIR motif is conserved and consists of an 11-amino acid sequence. p62 and NBR1 are involved in bone remodeling and T-cell activation. The LIR-ATG8 interaction is essential for autophagic degradation. pSelective autophagy is a more specific process than previously thought, with autophagic adapter proteins like p62 and NBR1 playing key roles. These proteins are selectively degraded by autophagy and act as cargo receptors for ubiquitinated substrates. They interact with the autophagosomal marker protein LC3 via a LIR motif, and their ability to polymerize and recognize substrates is essential for efficient selective autophagy. These features are conserved across species, including the yeast Cvt pathway and C. elegans P granules. Selective autophagy regulates cell signaling, affecting oxidative stress, tumorigenesis, and immunity. Autophagy is an evolutionarily conserved process that sequesters and transports organelles and macromolecules to lysosomes for degradation. It is involved in nutrient recycling during starvation and in the innate immune response against pathogens. Yeast genetics has been crucial in understanding autophagy machinery, with 34 ATG genes identified. Two ubiquitin-like conjugation systems are part of the conserved autophagic machinery, and four additional protein complexes are required for autophagy. In mammals, the ULK1 complex and class III PtdIns 3-kinase regulate autophagosome formation. ATG8 proteins, such as LC3 and GABARAP, are conjugated to phosphatidylethanolamine (PE) and serve as autophagic markers. Chaperone-mediated autophagy (CMA) degrades soluble proteins with a KFERQ motif. The Cvt pathway in yeast delivers lysosomal enzymes to the vacuole. Selective autophagy targets protein inclusions, organelles, and pathogens, including aggrephagy (degradation of protein aggregates), pexophagy (peroxisomes), mitophagy (mitochondria), xenophagy (bacteria/viruses), reticulophagy (surplus ER), and ribophagy (ribosomes). p62 and NBR1 are selective autophagy substrates and cargo receptors. p62 is a 440-amino acid protein with a PB1 domain, ZZ domain, LIR motif, and UBA domain. It binds to ubiquitin and is involved in autophagic degradation of protein aggregates, misfolded proteins, and damaged mitochondria. NBR1 is also a selective autophagy substrate and cargo receptor, with a similar domain structure to p62 but also containing a FW domain. The LIR motif is crucial for p62 and NBR1 interaction with LC3/GABARAP family proteins. The LIR motif is conserved and consists of an 11-amino acid sequence. p62 and NBR1 are involved in bone remodeling and T-cell activation. The LIR-ATG8 interaction is essential for autophagic degradation. p