Atg16l1, also known as autophagy related 16-like 1, is a key player in autophagy. It is part of the ATG12-ATG5/Atg16l1 complex, which, like its yeast counterpart, is crucial for autophagosome formation. Autophagy is a fundamental cellular catabolic process that recycles cytoplasmic components and plays essential roles in development, immunity, and cell death [1,2].

In colorectal cancer, deletion of Atg16l1 in engineered murine colon cancer organoids inhibits tumor growth in primary and metastatic niches, due to increased sensitivity to IFN-γ-mediated immune pressure. High tumor expression of Atg16l1 is associated with poor response to anti-PD-L1 therapy in KRAS-mutant tumors [3].

In metabolic dysfunction-associated steatohepatitis (MASH), macrophage-specific Atg16l1 knockout exacerbates MASH, while transgenic overexpression attenuates it. Atg16l1 knockout inhibits macrophage lipophagy, leading to downstream effects promoting hepatic steatosis and stellate cell activation [4].

In conclusion, Atg16l1 is essential for autophagosome formation and autophagy. Studies using gene knockout mouse models have revealed its significance in diseases such as colorectal cancer and MASH. In colorectal cancer, it influences anti-tumor immunity, and in MASH, it modulates macrophage-related inflammation and metabolism through lipophagy, providing insights into potential therapeutic targets for these diseases.