LCL768 is a ceramide analogue that attenuates PARKIN succinylation, thereby promoting PARKIN activation and mitophagy. It induces the accumulation of CerS1-mediated endogenous C18-ceramide in mitochondria, facilitating mitophagy through DRP1 activation via C644 site nitrosylation. Additionally, LCL768 alters mitochondrial metabolism, depleting fumarate and inhibiting tumor growth. Furthermore, it ameliorates sensorimotor deficits in neurodegenerative diseases such as ALS.