CLPB is a mitochondrial intermembrane space AAA+ ATPase that functions as an ATP-dependent protein disaggregase critical for mitochondrial proteostasis. Its primary role involves maintaining solubility of key mitochondrial proteins and preventing protein aggregation under stress conditions 1. CLPB mechanistically maintains mitochondrial cristae structure through interaction with the cristae-shaping protein OPA1, and it interacts with multiple quality control factors including PARL, YME1L1, and HAX1 to coordinate intermembrane space and inner membrane protein quality control 21. Beyond protein disaggregation, CLPB participates in mitochondrial-mediated antiviral immunity by activating RIG-I signaling and promoting IFNB1 and IL-6 production, and plays a role in granulocyte differentiation. CLPB shows preferential attachment to mitochondrial RNA granules and translation components 3. Clinically, CLPB mutations cause severe mitochondrial disorders including 3-methylglutaconic aciduria types 7A and 7B, and severe congenital neutropenia 9 4. CLPB deficiency leads to stress-specific protein aggregation in the intermembrane space, impairing SPY complex function and disrupting mitochondrial quality control networks 1. Additionally, CLPB dysfunction contributes to mitochondrial cardiomyopathy through proteostasis disruption affecting cardiac energetics 5. Importantly, in acute myeloid leukemia, CLPB upregulation promotes venetoclax resistance, making CLPB inhibition a promising therapeutic strategy to resensitize resistant AML cells to apoptosis 2.