Given a reported role for LIS1 in dynein-mediated spindle orientation (Faulkner et al., 2000; Pawlisz et al., 2008; Siller and Doe, 2009; Xie et al., 2013; Yingling et al., 2008), and the importance of spindle orientation in neuronal cell differentiation and generation of progenitors (Bershteyn et al., 2017; Fish et al., 2006; Götz and Huttner, 2005), another potential confounding cause for lissencephaly is dysfunctional spindle orientation, in addition to defects in nuclear migration (Figure 1B; see Box 2). This evidence concerns the gene PAFAH1B1 and Lissencephaly.