PHB1 (prohibitin 1) is a multifunctional protein primarily localized to the mitochondrial inner membrane where it forms heterodimeric complexes with PHB2 and plays critical roles in mitochondrial integrity and cellular metabolism 1. PHB1 regulates mitochondrial DNA (mtDNA) release by controlling permeability across the inner mitochondrial membrane, with PHB1 deficiency leading to increased cytoplasmic mtDNA release and inflammatory responses including elevated IL-1β levels 1. Under physiological conditions, PHB1 tethers proteins AFG3L2 and SPG7 to prevent mitochondrial permeability transition pore opening, but inflammatory stress downregulates PHB1 expression, disrupting this protective mechanism 1. In mitophagy regulation, PHB1 functions as an Atg8 receptor in yeast through conserved AIM/LIR-like motifs and negatively regulates Atg32 processing 2. PHB1 also supports oxidative phosphorylation through K63-linked ubiquitination at lysine 186, which promotes its mitochondrial translocation and interaction with Akt 3. Additionally, PHB1 suppresses ATF4 transcription in endothelial cells, affecting serine and one-carbon metabolism pathways 4. Genome-wide studies have identified PHB1 as relevant to aging-related traits, suggesting its broader role in healthy aging processes 5. These findings establish PHB1 as a key regulator of mitochondrial homeostasis, immune responses, and metabolic processes.