Diablo IAP-binding mitochondrial protein

DIABLO (Diablo IAP-binding mitochondrial protein) is a mitochondrial apoptotic regulator that promotes programmed cell death by antagonizing inhibitor of apoptosis proteins (IAPs), particularly XIAP and BRUCE (UniProt: Q9NR28). It functions by promoting ubiquitination and degradation of XIAP through the proteasome pathway and by disrupting IAP-caspase interactions, thereby enabling caspase-3 and caspase-9 activation in the cytochrome c/Apaf-1 apoptotic axis (UniProt: Q9NR28).

DIABLO is a mitochondrial protein involved in cell death regulation. A rare variant in DIABLO is associated with autosomal dominant sensorineural hearing loss (DFNA64), but the protein's primary role centers on apoptosis control (UniProt: Q9NR28).

This protein is upregulated in Alzheimer's disease brain tissue. Human post-mortem AD brain samples showed elevated DIABLO levels compared to age-matched controls (mean log2 fold-change: 0.91) in a TMT-labeled proteomics study across subcellular fractions (Chaparral AD proteomics). Increased DIABLO expression may reflect heightened apoptotic signaling in AD pathology, consistent with neuronal cell death processes observed in the disease.