Epg5, also known as ectopic P-granules 5 autophagy tethering factor or ectopic P-granules autophagy protein 5 homolog (C. elegans), is a crucial regulator in the autophagy pathway. It is involved in the fusion of autophagosomes with late endosomes or lysosomes during macroautophagy, which is essential for maintaining cellular homeostasis by clearing damaged organelles and misfolded proteins [2]. The study of genetic models, such as knockout zebrafish and KO mouse models, has been valuable for understanding its functions.

In KO mouse models, Epg5 deficiency leads to primary ovarian insufficiency. This is due to the blockage of autophagic flux, resulting in the accumulation of WT1, an essential transcription factor for granulosa cells, which disrupts their differentiation [1]. In zebrafish, epg5 -/- mutants show higher levels of the Lc3-II autophagy marker, indicating dysfunctional autophagy similar to that in Vici syndrome. These mutants also display impaired motility, muscle thinning, and morphological alterations in gonads and heart as they age [2]. Additionally, epg5 knockout in zebrafish males impairs reproductive success and courtship behavior [3].

In conclusion, Epg5 is essential for autophagosome-lysosome fusion and normal autophagic function. Studies using gene knockout models, especially in mice and zebrafish, have revealed its significance in reproductive processes, such as ovarian function in mice and male reproductive performance in zebrafish, as well as its association with Vici syndrome-related phenotypes. Understanding Epg5's functions provides insights into the mechanisms underlying autophagy-related diseases and reproductive disorders.