Cardiolipin (CL), an essential phospholipid, is localized in the mitochondrial inner membrane, where it plays a critical role in oxidative phosphorylation (OXPHOS) and energy metabolism. This study reviews current findings on cardiolipin's function within neurodegenerative diseases (NDDs), focusing on Alzheimer's and Parkinson's diseases, along with Barth Syndrome. Using lipidomics and protein-lipid interaction analysis, we examine the role of CL in mitochondrial integrity and neuronal function. The primary objective is to analyze how alterations in CL composition and distribution can serve as biomarkers and therapeutic targets for NDDs. Results highlight significant insights into the potential for CL-targeted therapies.