PPCDC (phosphopantothenoylcysteine decarboxylase) catalyzes the decarboxylation of 4'-phosphopantothenoylcysteine to 4'-phosphopantetheine, a critical enzymatic step in coenzyme A (CoA) biosynthesis 1. This reaction is essential for CoA production, a universal cofactor required for over 100 metabolic reactions including long-chain fatty acid activation and mitochondrial energy metabolism 2. The enzyme contains an FMN-binding domain and functions in the cytosol as part of a conserved five-step pathway involving four enzymes 1. PPCDC deficiency causes severe pathology through energy depletion. Biallelic PPCDC variants (p.Thr53Pro and p.Ala95Val) cause ultra-rare, fatal autosomal-recessive dilated cardiomyopathy, with the Thr53 residue critical for FMN binding and Ala95 affecting protein stability 1. Patient fibroblasts show ~50% CoA reduction, mitochondrial respiratory defects, and reliance on glycolytic ATP synthesis 1. CoA limitation represents a critical cardiomyopathy pathomechanism, with potential therapeutic benefit from vitamin B5 derivatives 2. Additionally, PPCDC genetic variation associates with chemotherapy-related amenorrhea risk in breast cancer patients 3, and the CoA biosynthesis pathway regulates yeast lifespan 4. PPCDC represents the second CoA biosynthesis enzyme linked to cardiac disease, contrasting with neurological manifestations of first and last pathway enzyme defects 5.