ATG14, short for autophagy-related 14, is a key regulator of autophagy. It is an essential component for the fusion of autophagosomes with lysosomes in the autophagy-lysosomal degradation system. Autophagy is a crucial cellular process involved in maintaining cellular homeostasis, and ATG14's role in this pathway makes it biologically significant. Genetic models, such as gene knockout mouse models, have been valuable in studying its functions [1,3,4].

In macrophages, ATG14 is crucial for autophagy function. In human and mouse atherosclerotic plaques, macrophages show impaired autophagy with reduced ATG14 expression. Overexpressing ATG14 in macrophages promotes autophagosome-lysosome fusion, lipid degradation, and alleviates atherosclerotic lesions by inhibiting inflammation and upregulating Treg cells [1]. In hepatocytes, ATG14 is enriched on lipid droplets. Its deficiency decreases triglyceride hydrolysis, indicating its role in hepatic lipid droplet homeostasis [3]. Also, ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover, and coronavirus hijacks the STX18-ATG14 axis-regulated lipophagy to evade anti-viral effects [2,4].

In conclusion, ATG14 plays essential functions in autophagy, especially in autophagosome-lysosome fusion and lipid metabolism. Studies using gene knockout models have revealed its significance in diseases like atherosclerosis, highlighting its potential as a therapeutic target for such conditions.