Cysteine protease ATG4A (ATG4A)

Cysteine protease ATG4A (ATG4A) is an enzyme critical in the process of autophagy. It processes and deconjugates mammalian ATG8 homolog proteins (e.g., GABARAPL2), enabling their attachment (lipidation) and removal from autophagosomal membranes, which is vital for autophagosome formation, maturation, and recycling[5][4][1]. ATG4A influences key pathways in cellular homeostasis, including the AMPK and Akt signaling axes, and plays roles in cell proliferation, apoptosis, and clearance of damaged organelles[1][6]. Elevated ATG4A expression has been linked to cancer progression, tamoxifen resistance in breast cancer, cellular responses to oxidative stress, and diseases involving defective autophagy, such as neurodegeneration and cataract[2][1][3]. Genetic studies highlight both redundant and unique roles among ATG4 family members, suggesting complexity in therapeutic targeting[3][4]. There are no approved drugs that specifically inhibit ATG4A, but it is a subject of investigation as a potential selective target in cancer and other autophagy-implicated diseases[3][5].

Other names

Cysteine protease ATG4AAutophagy related 4A cysteine peptidaseATG4AAPG4AAUTL2Autophagin-2HsAPG4AhAPG4AAUT-like 2 cysteine endopeptidaseAutophagy-related cysteine endopeptidase 2Autophagy-related protein 4 homolog AAPG4 autophagy 4 homolog AATG4 autophagy related 4 homolog AAUT-like 2autophagin 2

Inhibitors or modulators block the proteolytic activity of ATG4A, disrupting autophagosome formation by preventing ATG8 protein processing and lipidation[3]. Knockdown or inhibition sensitizes cancer cells to chemotherapies by blocking protective autophagy[2].