MAP1LC3A (LC3) is a ubiquitin-like protein essential for autophagosome formation and maturation. During macroautophagy, LC3 is lipidated and conjugated to phagophore membranes, where it serves as a membrane scaffold 1. LC3 functions in the early elongation stages of autophagosome formation, while the related GABARAP/GATE-16 subfamily handles later maturation steps [UniProt]. Through LC3-interacting region (LIR) motifs, cargo receptors bind lipidated LC3 to enable selective autophagy of specific substrates including mitochondria, protein aggregates, and endoplasmic reticulum subdomains 23. Beyond canonical autophagy, LC3 participates in LC3-associated phagocytosis (LAP), a non-canonical pathway where LC3 conjugates to phagosome membranes following pathogen or dying cell recognition, contributing to immune regulation and inflammatory responses 4. LC3 lipidation is tightly regulated—ATG7 acetylation suppresses LC3 conjugation, while deacetylation drives both macroautophagy and LC3-associated microautophagy in response to cellular stress 5. LC3 conversion (LC3-I to LC3-II) serves as a widely-used autophagy marker, though careful interpretation is required as LC3-II itself undergoes lysosomal degradation 6. Given autophagy's dual role in cancer—simultaneously supporting tumor cell survival and enabling therapeutic cell elimination—LC3-targeting approaches remain therapeutically relevant 7.