Sorting out non-canonical autophagy

Canonically, LC3 lipidation has been associated with autophagy pathways but it becomes increasingly clear that this modification can also occur during autophagy-unrelated processes. In this issue, Florey and colleagues find that the WD40 domain of ATG16L1 is dispensable for LC3 lipidation during starvation-induced autophagy but required for its lipidation during several other membrane-based processes that are different from autophagy. This finding opens the door for the analysis of the functions of LC3 lipidation in these pathways.