LRRK2 is a key protein that controls lysosomal and synaptic vesicle (SV) protein trafficking. Mutations in this gene have been associated with familial Parkinson's disease. Loss-of-function mutations in LRK-1, the C. elegans homolog of LRRK2, are known to have SV protein trafficking defects. To identify factors acting alongside or downstream of LRK-1, we investigated the role of SYD-2/Liprin-? due to its known roles in SV and lysosomal protein localization. We show that like LRK-1, SYD-2 regulates biogenesis of SV protein transport carriers. However, unlike
lrk-1 mutants,
syd-2 mutants do not affect the polarized distribution of SV proteins. Interestingly,
syd-2 can suppress the dendritic mis-trafficking of SV proteins observed in
lrk-1 mutants, similar to the clathrin adaptor protein 1 (AP-1) complex. Additionally, we see that unlike wildtype, loss-of-function mutants of
lrk-1 and
syd-2 show presence of lysosomal proteins in C. elegans axons. However,
syd-2 does not suppress lysosomal positioning defects observed in
lrk-1 mutants. These data suggest a role for SYD-2 in neuronal protein trafficking where it acts in the same pathway as LRK-1 to regulate SV protein positioning, while acting independently of LRK-1 for lysosomal protein distribution.