Cysteine protease that plays a key role in cytoplasm to vacuole transport (Cvt) and autophagy by mediating both proteolytic activation and delipidation of ATG8 (PubMed:11038174, PubMed:11100732, PubMed:11149920, PubMed:11904149, PubMed:16680092, PubMed:18701704, PubMed:18725539, PubMed:8050581, PubMed:8224160, PubMed:9649430, PubMed:28330855, PubMed:28821724, PubMed:28704456). Required for selective autophagic degradation of the nucleus (nucleophagy) as well as for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production (PubMed:11038174, PubMed:11100732, PubMed:11149920, PubMed:11904149, PubMed:16680092, PubMed:18701704, PubMed:18725539, PubMed:8050581, PubMed:8224160, PubMed:9649430). The protease activity is required for proteolytic activation of ATG8: cleaves the C-terminal amino acid of ATG8 to reveal a C-terminal glycine (PubMed:11038174, PubMed:11100732, PubMed:11149920, PubMed:11904149, PubMed:16680092, PubMed:18701704, PubMed:18725539, PubMed:8050581, PubMed:8224160, PubMed:9649430). ATG8 ubiquitin-like activity requires the exposure of the glycine at the C-terminus for its conjugation to phosphatidylethanolamine (PE) and its insertion to membranes, which is necessary for autophagy (PubMed:11038174, PubMed:11100732, PubMed:11149920, PubMed:11904149, PubMed:16680092, PubMed:18701704, PubMed:18725539, PubMed:8050581, PubMed:8224160, PubMed:9649430). The ATG8-PE conjugate mediates tethering between adjacent membranes and stimulates membrane hemifusion, leading to expansion of the autophagosomal membrane during autophagy (PubMed:17632063). In addition to the protease activity, also catalyzes deconjugation of PE-conjugated forms of ATG8 during macroautophagy: ATG8 delipidation is required to release the protein from membranes, which facilitates multiple events during macroautophagy, and especially for efficient autophagosome biogenesis, the assembly of ATG9-containing tubulovesicular clusters into phagophores/autophagosomes, and for the disassembly of PAS-associated ATG components (PubMed:22240591, PubMed:22652539, PubMed:28330855, PubMed:28821724, PubMed:28704456). ATG8 delipidation by ATG4 also recycles ATG8-PE generated on inappropriate membranes to maintain a reservoir of unlipidated ATG8 that is required for autophagosome formation at the PAS (PubMed:22240591, PubMed:22652539). [protein]-C-terminal L-amino acid-glycyl-phosphatidylethanolamide + H2O = [protein]-C-terminal L-amino acid-glycine + a 1,2-diacyl-sn-glycero-3-phosphoethanolamine Inhibited by N-ethylmaleimide. Interacts with ATG8 (PubMed:16680092, PubMed:9649430, PubMed:28287329, PubMed:28330855, PubMed:28821724). Interacts with TUB1 and TUB2 (PubMed:9649430). Expression is induced upon starvation, through the action of transcription factors GCN2 and GCN4. The APEAR motif (ATG8-PE association region) plays a key role in ATG4 recruitment to autophagosomal membranes and ATG8 deconjugation (PubMed:28330855). The LIR (LC3-interacting region act cooperatively) and APEAR motifs for the interaction with ATG8 (PubMed:28287329, PubMed:28330855). Phosphorylation at Ser-307 by ATG1 inhibits autophagy: it takes place on autophagosome membranes and decreases its interaction with ATG8, thereby impairing deconjugation of PE-conjugated forms of ATG8. Formation of a disulfide bond between Cys-338 and Cys-394 leads to reduced autophagy (PubMed:25483965). The disulfide bond is reduced by thioredoxin (PubMed:25483965). Present with 3300 molecules/cell in log phase SD medium. Belongs to the peptidase C54 family. Extended N-terminus. Extended N-terminus.