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Autophagy protein 5 (ATG5) is a ubiquitin-like protein encoded by the *ATG5* gene on human chromosome 6. It forms a covalent complex with ATG12, which then associates with ATG16L1, creating the ATG12–ATG5–ATG16L1 complex crucial for autophagosome membrane elongation. ATG5 is activated by various protein kinases and transcription factors under cellular stress. Beyond its canonical autophagic functions, ATG5 can regulate apoptosis through calpain-mediated cleavage and mitochondrial translocation, participate in cell cycle arrest after DNA damage (G2/M arrest and mitotic catastrophe), and is involved in immune cell functions such as macrophage polarization and T-cell survival. ATG5 dysregulation is implicated in diverse human diseases, including cancer, neurodegenerative conditions, autoimmune and inflammatory diseases, and it serves as a key biomarker for autophagy-related cellular activity[1][2][3][4][5].
Activation or inhibition of autophagy by modulating ATG5 complex formation (either via upstream regulators, direct protein modulation, or mimicking cleavage-induced pro-apoptotic actions); Induction of apoptosis via calpain-mediated cleavage and mitochondrial targeting.
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