Early onset Parkinson’s disease (EOPD) with an age-of-onset <50 years, is commonly inherited pointing towards a genetic cause. Amongst the roughly 15 PARK genes that are mutated in EOPD, PINK1 and Parkin are frequently harbouring loss-of-function mutations. Research in the past decade has unveiled the role of PINK1 and Parkin in mitochondrial turnover, and our work has explained how PINK1 and Parkin are activated at the molecular level. Together, this has led to detailed molecular movies of the earliest steps of mitophagy, explaining how damaged mitochondria are tagged for destruction. The molecular movies have further enabled a clear view of where and how disease modulating small molecule drugs could act, and which patient subpopulations would benefit from such emerging treatments. Our Shake-It-Up / Michael J Fox Foundation funded project proposes to utilise the National Drug Discovery Centre to identify these targeted, first-in-class small molecules.