PMPCB encodes the catalytic subunit of mitochondrial processing peptidase (MPP), an essential protease that cleaves mitochondrial targeting sequences from newly imported precursor proteins 1. The enzyme preferentially recognizes and cleaves after arginine residues at the P2 position [UniProt annotation]. PMPCB is particularly important for PINK1 turnover, coupling PINK1 mitochondrial import and cleavage to enable subsequent proteolysis, thereby regulating mitochondophagy 2. Dysfunction of PMPCB impairs iron-sulfur cluster biogenesis, a critical pathway for multiple cellular processes 1. Biallelic PMPCB mutations cause early-childhood neurodegeneration with cerebellar atrophy and developmental regression, characterized by accumulation of mitochondrial precursor proteins and respiratory chain dysfunction 13. In kidney disease, epigenetic dysregulation of PMPCB contributes to persistent mitochondrial dysfunction, oxidative stress, and fibrosis progression in both acute and chr7 kidney injury 4. PMPCB overexpression alleviates LPS-induced oxidative stress and inflammation in renal epithelial cells 5. Clinically, PMPCB represents a therapeutic vulnerability in EpCAM+ hepatocellular carcinoma (HCC); PMPCB silencing suppresses Wnt/β-catenin signaling via mitochondrial reactive oxygen species production, inducing apoptosis 6. Additionally, PMPCB knockdown sensitizes HCC cells to sorafenib therapy by enhancing PINK1-Parkin-mediated mitophagy and downregulating anti-apoptotic MCL-1 2.