Barth syndrome (BTHS) is a rare, x-linked, mitochondrial disease caused by recessive loss-of-function mutations in the gene TAFAZZIN, which encodes the tafazzin protein. Tafazzin is a nuclear-encoded transferase that is trafficked to the inner mitochondrial membrane where it remodels monolysocardiolipin (MLCL) to mature cardiolipin (CL). CL is a critical phospholipid involved in maintenance of mitochondrial membrane fluidity, osmotic stability, and efficient respiratory chain function. Our lab uses differentiated patient derived iPSCs and a mouse model of BTHS to better understand the underlying mechanisms of this disease and how it impacts heart and skeletal muscle function. We are also developing an optimized AAV mediated gene therapy delivery approach to treat BTHS.