Autophagy-related 4B (ATG4B), also known as autophagin-1, is a cysteine protease and a member of the C54 protease family with dual roles in the progression of autophagy. It catalyzes the irreversible proteolytic cleavage of human homologs of yeast atg8 belonging to the microtubule-associated proteins 1 (MAP1)A/B-light chain 3 (LC3) and the GABA receptor-associated protein (GABARAP) subfamilies, including LC3, GATE16, GABARAP, and ATG8L, to expose a C-terminal glycine residue that is essential to formation of the autophagosome. It also catalyzes the reversible deconjugation of phosphatidylethanolamine from C-terminal glycine lipid-conjugated atg8 homologs. ATG4B expression is increased in CD34+ chronic myeloid leukemia (CML) stem and progenitor cells and knockdown of ATG4B expression increases accumulation of LC3-II and p62, indicating impaired autophagy, and reduces the viability and inhibits proliferation of CD34+ CML cells. Atg4-/- mice exhibit systemic decreases in basal and induced autophagy as well as increased susceptibility to colitis induced by dextran sodium sulfate (DSS) and pulmonary fibrosis induced by bleomycin .
