Atg16l1, an autophagy-related gene in higher eukaryotes, is similar to yeast Atg16. It is part of the ATG12-ATG5/ATG16L1 complex, which is essential for autophagosome formation as it catalyzes the lipidation of Atg8 (MAP1LC3/LC3 in higher eukaryotes) in autophagy [1,2]. Autophagy is a fundamental cellular catabolic process crucial for development, immunity, and cell death, recycling cytoplasmic components like misfolded proteins, dysfunctional organelles, and microbial invaders [2].

In mice, Atg16l1 hypomorphism or cell-specific ablation has shown various consequences. For instance, 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, revealing its role in suppressing anti-tumor immunity in colorectal cancer [3]. In myeloid-specific Atg16l1-deficient mice, macrophage-specific Atg16l1 knockout exacerbates metabolic dysfunction-associated steatohepatitis (MASH) by inhibiting lipophagy, while overexpression attenuates MASH, indicating its importance in MASH progression [4].

In conclusion, Atg16l1 is essential for autophagosome formation in autophagy. Gene-knockout mouse models have revealed its significance in diseases such as colorectal cancer and MASH, where it plays roles in immune evasion and disease progression respectively. Understanding Atg16l1 through these models provides insights into disease mechanisms and potential therapeutic targets.