Ectopic P granules protein 5 homolog (EPG5)

Ectopic P granules protein 5 homolog (EPG5) is a large metazoan-specific coiled-coil protein (~290 kDa) that functions as a tethering factor in macroautophagy, specifically mediating the fusion between autophagosomes and lysosomes to ensure specificity and prevent mistargeting. EPG5 interacts preferentially with the GABARAP subfamily of ATG8 proteins through unique tandem LC3-interacting regions (LIR motifs) to facilitate and regulate autophagosome–lysosome fusion. Deficiency in EPG5 leads to mistargeting, impaired autophagic flux, and accumulation of dysfunctional vesicles, contributing to the pathogenesis of Vici syndrome—a severe multisystem disorder affecting brain, immune system, heart, skin, and eyes. EPG5 also plays a role in cellular immune responses to intracellular pathogens. There are currently no drugs targeting EPG5 directly, and mutations are primarily relevant as diagnostic biomarkers for Vici syndrome.

Other names

EPG5Ectopic P-granules 5 autophagy tethering factorKIAA1632hEPG5HEEW1VICISEctopic P-granules autophagy protein 5 homolog

Not applicable; no drugs specifically modulate EPG5 function as a primary target