LC3-associated phagocytosis: A critical link between cellular clearance and immune homeostasis in disease

Light Chain 3 (LC3)-associated phagocytosis (LAP) represents a unique noncanonical pathway that converges the core machinery of autophagy with the phagocytic uptake of extracellular cargo. A defining feature of LAP is the recruitment and conjugation of LC3 family proteins to the phagosome membrane, which facilitates the recognition and lysosomal degradation of diverse targets, including pathogens, dying cells, soluble ligands, and protein aggregates. Disruption of LAP can impair phagocytic cargo clearance, leading to the accumulation of undigested phagocytic cargo, chronic inflammation, and tissue damage. In this review, we summarize the molecular mechanisms that regulate LAP and discuss its roles in immunity to bacterial, fungal, and parasitic infections. A key focus is elucidating the fundamental regulatory differences between canonical autophagy and LAP. Furthermore, we also discuss the roles of LAP in innate immunity, inflammation, and disease. Importantly, we provide a summary of various endogenous and pharmacological inducers of LAP. By integrating this knowledge, we aim to propose potential therapeutic strategies that leverage the modulation of LAP for the treatment of related diseases.