BNIP3 (BCL2 interacting protein 3) is a mitochondrial quality control protein that regulates selective autophagy of mitochondria (mitophagy) and cell death. As a BH3-only family member, BNIP3 can overcome BCL2-mediated apoptosis suppression and induce cell death through intrinsic apoptotic pathways 1. BNIP3 functions as a mitophagy receptor that tethers mitochondria to autophagic machinery; cells lacking both BNIP3 and its homolog NIX exhibit complete loss of mitophagy capacity 2. BNIP3-mediated mitophagy is regulated by the SIRT1-FOXO3 transcriptional axis 3 and SIRT3 4, with stability maintained through PGAM5-mediated protection from ubiquitin-proteasome degradation 5. BNIP3 responds to hypoxia and mitochondrial dysfunction, serving as a sensor for mitochondrial import stress that can switch between PINK1/Parkin and NIX/BNIP3 mitophagy pathways 6. Clinically, BNIP3 overexpression contributes to doxorubicin-induced cardiotoxicity 7 and cancer-associated muscle wasting 5, while BNIP3-mediated mitophagy protects against ferroptosis by regulating mitochondrial reactive oxygen species 2. AMPK differentially regulates BNIP3 and NIX mitophagy, inhibiting programmed mitophagy while enhancing mitophagy of dysfunctional mitochondria 8.