In this research project, we have revealed that LRRK1 plays an important role in the regulation of mitotic spindle orientation. It is known that the regulation of the cell division axis by mitotic spindle orientation is required for proper epithelial morphogenesis. We recently found that leucine-rich repeat kinase 1 (LRRK1), a member of ROCO family kinase, is activated on mitotic centrosome in a manner dependent on the phosphorylation by PLK1 and CDK1, and then regulates spindle orientation. We identified the centrosomal protein CDK5RAP2, a human homologue of Drosophila Centrosomin, as a substrate of LRRK1. CDK5RAP2 is known to regulate centrosome maturation. We found that LRRK1 phosphorylates CDK5RAP2 in its N-terminal γ-tubulin-binding motif (CM1 motif), thus promoting the interaction of CDK5RAP2 with γ-tubulin. LRRK1 phosphorylation of CDK5RAP2 is necessary for CDK5RAP2-dependent MT nucleation (Nature Cell Biology, 2015: Cell Cycle, 2015). Thus, our findings provide evidence that LRRK1 regulates mitotic spindle orientation downstream of PLK1 and CDK1 through CDK5RAP2-dependent centrosome maturation, leading to the proper formation of lumen.