Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common genetic cause of Parkinson’s disease (PD). In addition, sequence variations at the LRRK2 locus increase risk for developing sporadic PD, thus highlighting the crucial role for LRRK2 in both disease entities. Pathogenic point mutations in LRRK2 segregate with familial disease in an autosomal-dominant manner, indicating a toxic gain-of-function phenotype. Indeed, most mutations increase the kinase activity of LRRK2, and this has spurred great hope for novel PD drug development approaches. However, no consistent LRRK2 kinase substrates have been identified thus far, and the cellular role(s) of LRRK2 have remained largely unknown. Over the past years, we have investigated the cellular function(s) of LRRK2 using a variety of approaches. We have used transient expression of wildtype or mutant proteins in various tissue culture cell types, or analyzed effects of endogenous LRRK2 using patient-derived cells from either healthy controls or from patients with PD due to LRRK2 mutations. Our data indicate that pathogenic LRRK2 functions at the late endosome in a manner dependent on kinase activity. The late endosome comprises a major intracellular trafficking hub, and deficits can have profound effects on both endocytic and autophagic trafficking events. Interestingly, we found that the observed LRRK2-mediated alterations were mimicked by NAADP, which triggers calcium release from acidic stores, and blocked by an NAADP antagonist. Subsequent studies highlighted a role for the NAADP-sensitive TPC2 channels in the LRRK2-mediated events, with mechanistic implications for PD being related to altered calcium-dependent trafficking to and from endolysosomal stores. The characteristics of the link between LRRK2 and TPC2 function, and molecular insights into its regulation will be discussed. Together, our data indicate that TPC2 channels as well as modulators thereof may comprise additional promising drug targets for LRRK2-linked PD.