Elsevier established a free COVID-19 resource center in January 2020, offering English and Mandarin information on the virus. The center is hosted on Elsevier Connect, and research from it is freely available in PubMed Central and other repositories for research use. The article reviews the LC3 conjugation system in mammalian autophagy. LC3, an autophagosomal orthologue of yeast Atg8, is modified by lipidation to form LC3-II, a marker of autophagosomes. It plays a role in autophagy, cell differentiation, microbial infection, cancer, and neuromuscular diseases. Other Atg8 homologues, GABARAP and GATE-16, are also modified by similar mechanisms. The study highlights the molecular mechanisms of LC3 modification, its interaction with Atg12-conjugation, and the lipidation and delipidation cycles mediated by hAtg4B. It also discusses recent findings on the roles of LC3 in various diseases, including its involvement in microbial infection, cancer, and neuromuscular disorders. The review emphasizes the functional divergence among LC3, GABARAP, and GATE-16, and their roles in autophagy and disease.Elsevier established a free COVID-19 resource center in January 2020, offering English and Mandarin information on the virus. The center is hosted on Elsevier Connect, and research from it is freely available in PubMed Central and other repositories for research use. The article reviews the LC3 conjugation system in mammalian autophagy. LC3, an autophagosomal orthologue of yeast Atg8, is modified by lipidation to form LC3-II, a marker of autophagosomes. It plays a role in autophagy, cell differentiation, microbial infection, cancer, and neuromuscular diseases. Other Atg8 homologues, GABARAP and GATE-16, are also modified by similar mechanisms. The study highlights the molecular mechanisms of LC3 modification, its interaction with Atg12-conjugation, and the lipidation and delipidation cycles mediated by hAtg4B. It also discusses recent findings on the roles of LC3 in various diseases, including its involvement in microbial infection, cancer, and neuromuscular disorders. The review emphasizes the functional divergence among LC3, GABARAP, and GATE-16, and their roles in autophagy and disease.