Mitochondrial Disaggregase (CLPB) Isoform 2

CLPB encodes mitochondrial disaggregase, an AAA+ ATPase that facilitates protein unfolding and disaggregation within mitochondria (UniProt: Q9H078-2). The protein functions as part of the mitochondrial protein quality control system, cooperating with other chaperones to resolve protein aggregates and maintain mitochondrial proteostasis.

Mitochondrial dysfunction and impaired protein quality control are implicated in neurodegenerative disease pathology. CLPB is expressed broadly but is particularly relevant to tissues with high oxidative demand, such as neurons, where mitochondrial integrity is essential for sustained energy production and cellular homeostasis.

In Alzheimer's Disease, CLPB isoform 2 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics: mean log2FC = 0.544, TMT-labeled quantitative proteomics across subcellular fractions). This upregulation likely reflects a compensatory response to increased mitochondrial stress and protein aggregation burden characteristic of AD pathology, suggesting that enhanced mitochondrial disaggregase activity may be mobilized in response to AD-associated proteotoxic challenges.