Autophagy Related 4B, Cysteine Peptidase (ATG4B), also known as Autophagy-related Protein 4 Homolog B (Apg4b), is a 393 amino acid (aa) cysteine protease with a predicted molecular weight of 45 kDa. The human protein shares 95% aa sequence identity with the mouse ortholog. ATG4B/Apg4b has a protease domain that is characteristic of papain superfamily cysteine proteases and an auxiliary domain of unknown function. Its catalytic activity is important for multiple steps during the catabolic autophagy pathway. During autophagy initiation, ATG4B/Apg4b is able to cleave LC3/MAP1LC3A/Apg8p3, GATE-16/Apg8p2, GABARAP/Apg8p1, and GABARAPL1 to expose a C-terminal glycine residue that is required for subsequent conjugation to phosphatidylethanolamine (PE). ATG4B/Apg4b also releases PE-conjugated LC3/MAP1LC3A/Apg8p3 from the outer membrane of autophagosomes prior to autolysosome formation. Due to its role as a regulator of autophagy, ATG4B/Apg4b has been linked to both physiological and pathological processes. It reportedly functions in skeletal homeostasis and adipocyte differentiation, and it may have a protective role against experimental colitis.