Mitophagy, the selective autophagy of damaged mitochondria, plays a critical role in maintaining mitochondrial quality control and cellular homeostasis. It is involved in various forms of regulated cell death (RCD), including apoptosis, pyroptosis, necroptosis, and ferroptosis, and has therapeutic potential in diseases such as tumors, degenerative diseases, and ischemia-reperfusion injury (IRI). Mitophagy can either inhibit or promote RCD depending on the context, with molecular mechanisms involving the regulation of key proteins like BCL2, BAX, and RIPK3. For example, mitophagy can reduce ROS levels and inhibit pyroptosis, while excessive mitophagy can lead to ferroptosis or necroptosis. In diseases such as Alzheimer's, Parkinson's, and diabetes, mitophagy-related RCD contributes to pathogenesis, and targeting mitophagy offers potential therapeutic strategies. In cancer, mitophagy can enhance drug resistance, but modulating mitophagy can also sensitize cancer cells to chemotherapy. In infectious diseases, mitophagy influences immune responses and viral replication. Overall, mitophagy's dual role in regulating RCD highlights its importance in disease mechanisms and therapeutic interventions. Further research is needed to clarify the molecular mechanisms and therapeutic applications of mitophagy in various diseases.Mitophagy, the selective autophagy of damaged mitochondria, plays a critical role in maintaining mitochondrial quality control and cellular homeostasis. It is involved in various forms of regulated cell death (RCD), including apoptosis, pyroptosis, necroptosis, and ferroptosis, and has therapeutic potential in diseases such as tumors, degenerative diseases, and ischemia-reperfusion injury (IRI). Mitophagy can either inhibit or promote RCD depending on the context, with molecular mechanisms involving the regulation of key proteins like BCL2, BAX, and RIPK3. For example, mitophagy can reduce ROS levels and inhibit pyroptosis, while excessive mitophagy can lead to ferroptosis or necroptosis. In diseases such as Alzheimer's, Parkinson's, and diabetes, mitophagy-related RCD contributes to pathogenesis, and targeting mitophagy offers potential therapeutic strategies. In cancer, mitophagy can enhance drug resistance, but modulating mitophagy can also sensitize cancer cells to chemotherapy. In infectious diseases, mitophagy influences immune responses and viral replication. Overall, mitophagy's dual role in regulating RCD highlights its importance in disease mechanisms and therapeutic interventions. Further research is needed to clarify the molecular mechanisms and therapeutic applications of mitophagy in various diseases.