Dysfunctional cilia underlie a number of human genetic conditions that affect multiple organs, causing blindness, heart disease, infertility, obesity and/or diabetes. One such ciliopathy is Bardet-Biedl Syndrome (BBS). There is considerable interest in understanding the molecular mechanisms involved in BBS as phenotypes associated with this disorder are commonly found within the general population. BBS1 is the most commonly mutated gene in BBS patients, and a single missense mutation causing a methionine to arginine substitution at position 390 (M390R) accounts for 80% of all BBS1 mutations. BBS1M390R is predicted to be highly disruptive due to the introduction of a positive charge into the hydrophobic core of the folded protein. We use the zebrafish to understand the functional properties of BBS1 and the disease mechanism of BBS1M390R. Analysis of BBS1 and BBS1M390R subcellular localization shows that BBS1M390R fails to localize to the centrosome. We also find that BBS1M390R maintains interaction with some, but not all, components of the BBSome complex, thereby likely disrupting its cellular function in cilia transport. To evaluate functional properties, suppression of knockdown defects (reduced Kupffer’s vesicle cilia and intracellular transport delays) was tested. We also examined the extent to which the interaction of BBS1 with BBS4, a component of the BBSome, influences stability and localization as well as describe recently generated BBS1 genetic lines.