PCCB encodes the beta subunit of propionyl-CoA carboxylase (PCC), a biotin-dependent mitochondrial enzyme essential for amino acid and fatty acid catabolism 1. As part of the PCC holoenzyme, PCCB transfers the carboxyl group from biotin to propionyl-CoA, converting it to methylmalonyl-CoA for entry into the tricarboxylic acid cycle 1. This enzyme processes propionyl-CoA derived from odd-chain fatty acids, branched-chain amino acids (isoleucine, threonine, methionine, valine), and other metabolites 1. Mutations in PCCB cause propionic acidemia type II, a rare autosomal recessive metabolic disorder characterized by toxic accumulation of propionyl-CoA and metabolites 2. This leads to mitochondrial energy dysfunction and oxidative stress, resulting in life-threatening complications including cardiac disease, neuropsychiatric symptoms, seizures, and metabolic decompensation 23. Emerging evidence suggests PCCB also contributes to schizophrenia risk through GABAergic pathway dysregulation via mitochondrial dysfunction 4. Recent therapeutic advances include mRNA-based replacement therapy (mRNA-3927), which demonstrated 70% reduction in metabolic decompensation events in phase 1/2 trials 5. Understanding PCCB's role in mitochondrial metabolism is crucial for developing effective therapies beyond current dietary management approaches.