PHB2 (prohibitin 2) is a mitochondrial inner membrane scaffold protein that serves as a critical mitophagy receptor mediating selective removal of damaged mitochondria. PHB2 promotes PINK1-PRKN/Parkin-dependent mitophagy through the PARL-PGAM5-PINK1 axis 1. Upon mitochondrial depolarization, PHB2 stabilizes PINK1 to facilitate Parkin recruitment and ubiquitination, with VDAC1 enhancing efficient PHB2 exposure at mitochondrial rupture sites 2. Beyond mitophagy, PHB2 regulates cellular energy metabolism by interacting with NDUFS1 to stabilize mitochondrial complex I and enhance oxidative phosphorylation (OXPHOS), promoting colorectal cancer cell proliferation 3. PHB2 also plays pathogenic roles in bacterial infections: S. Typhimurium exploits the SseJ-PHB2 axis to activate mitophagy for bacterial survival 4, while enterovirus 71 enhances autophagy through PHB2 during infection [UniProt summary]. Disruption of PHB2-mediated mitophagy contributes to disease pathogenesis. ALDH2 lactylation promotes PHB2 degradation, impairing mitophagy and exacerbating acute kidney injury 5. ANXA2 competitively inhibits PHB2-LC3B binding and promotes PHB2 proteasomal degradation via TRIM29, suppressing mitophagy after myocardial infarction 6. In ovarian cancer, lncRNA PART1 knockdown promotes PHB2 degradation, reducing mitophagy and conferring PARP inhibitor resistance 7.