LRRK2 and Parkinson disease: In neurons, LRRK2 R1441C knock in cells demonstrated a modest, but significantly reduced amount of synaptic vesicle endocytosis – suggesting mutation-dependent defects are conserved in vivo. Finally, using polygenic risk profiling we demonstrate an increased incidence of SNPs linked to Clathrin-dependent endocytosis genes in multiple PD patient cohorts, indicating this pathway is of direct relevance to disease aetiology.