Abstract Asymmetric cell divisions (ACDs) drive cell fate specification and the formation of complex tissue architectures. This often requires orienting the mitotic spindle to position daughter cells and/or segregate cell fate determinants. ACD’s drive the stratification and differentiation of the epidermis during embryogenesis. Additionally, oriented divisions have been observed to be associated with the production of hair follicle stem cell progenitors. However, whether spindle orientation is required for the production of these stem cells and how this is coupled to their cell fate remains unknown. During spindle positioning, astral microtubules of the mitotic spindle interact with specific regions of the cell cortex. However, we have an incomplete understanding of how microtubule dynamics and force production are controlled to precisely position mitotic spindles. My preliminary data shows that Kinesin Family Member 18B (KIF18B), which promotes microtubule catastrophes, is required for proper spindle orientation in cultured epidermal cells. Furthermore, KIF18B mutant mice have defects in the number and position of hair follicle stem cells, for the first time functionally linking spindle orientation to stem cell production. I hypothesize that KIF18B-induced microtubule depolymerization is required for spindle positioning, which in turn directs cell fate determination. Here I will examine both the molecular mechanism of KIF18B’s role in spindle orientation, and use KIF18B mutant mice to determine how spindle orientation is linked to production of hair follicle stem cells.