Epg5, also known as ectopic P-granules 5 autophagy tethering factor or ectopic P-granules autophagy protein 5 homolog (C. elegans), is crucial for autophagosome-lysosome fusion during macroautophagy [1,2,3,4]. This function is essential for maintaining normal autophagic flux, which is involved in processes like protein degradation and cellular homeostasis, and thus holds great biological importance. Genetic models, such as knockout zebrafish and KO mouse models, are valuable for studying Epg5 [4,5].

In mouse models, Epg5 knockout leads to subfertility in female mice with a primary ovarian insufficiency-like phenotype. It blocks autophagic flux, causing the accumulation of WT1 in granulosa cells, which disrupts GC differentiation [2]. In zebrafish epg5 -/- mutants, there are higher levels of the Lc3-II autophagy marker, indicating dysfunctional autophagy similar to Vici syndrome. These mutants also show muscle and gonad-related defects, as well as impaired motility and courtship behavior [4,5]. In Drosophila, impaired autophagic clearance due to Epg5-related proteotoxic stress is associated with seizure-like behaviors, and EPG5-mutated patients show a consistent epilepsy phenotype [3].

In conclusion, Epg5 is essential for autophagosome-lysosome fusion and normal autophagic flux. Model-based research, especially through Epg5 KO mouse and zebrafish models, has revealed its role in reproduction, muscle function, and neurological conditions like epilepsy and Vici syndrome. These findings contribute to understanding the underlying mechanisms of related diseases and may provide potential targets for treatment [2,3,4,5].