Autophagy-related 4B cysteine peptidase (ATG4B)

Autophagy-related 4B cysteine peptidase (ATG4B) is an intracellular cysteine protease critical for autophagy, especially for processing and recycling ATG8 family proteins (such as LC3 and GABARAP). ATG4B cleaves the C-terminal region of ATG8/LC3 homologs, exposing a glycine residue necessary for conjugation to phosphatidylethanolamine and anchoring in the autophagosome membrane. It is also responsible for delipidation, allowing recycling of ATG8 from completed autophagosomes. ATG4B is the most catalytically potent member of the human ATG4 family, with key roles in maintaining autophagic flux, cellular homeostasis, and responses to stress. Dysregulated ATG4B activity is implicated in cancer progression, inflammation (notably colitis), neurodegeneration, and infection. It is under investigation as a therapeutic target, primarily through autophagy inhibition in cancer and other disease contexts[1][2][3].

Other names

ATG4BAPG4BAUTL1HsAPG4Bautophagin-1autophagy-related protein 4 homolog B

Inhibitors block ATG4B's protease activity, preventing LC3/GABARAP processing, thereby inhibiting autophagosome formation and flux. Potential use in cancer by preventing autophagy-mediated survival of tumor cells[2].