PPCS (phosphopantothenoylcysteine synthetase) catalyzes the second step in coenzyme A biosynthesis from vitamin B5, conjugating cysteine to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine 123. The enzyme demonstrates preferential use of ATP over CTP as a cosubstrate 1. PPCS functions as a homodimer and localizes to the cytoplasm, nucleus, and cytosol, participating in acetyl-CoA biosynthetic processes and cardiac function [GO Annotations]. Biallelic mutations in PPCS cause autosomal-recessive dilated cardiomyopathy (DCM2C), a potentially fatal condition characterized by cardiac dysfunction without neurodegeneration, distinguishing it from defects in related CoA synthesis genes like PANK2 and COASY which cause neurodegeneration with brain iron accumulation 4. PPCS-deficiency represents a relatively new disease entity with unclear pathophysiology and currently no targeted therapeutic approaches. Patient-derived induced pluripotent stem cells have been generated as cellular models for investigating disease mechanisms and screening potential therapeutic compounds, offering promise for understanding PPCS-related cardiomyopathy and developing future treatments 4.