The Mis18 proteins (Mis18α, Mis18β, and M18BP1) are pivotal to the deposition of 
CENP-A at the centromere during cell cycle progression and are indispensable for 
embryonic development. Here, we show that Mis18α is critical for the 
proliferation of keratinocytes and stratification of the epidermis. Mice lacking 
Mis18α in the epidermis died shortly after birth, showing skin abnormalities 
like thin and translucent skin and defective skin barrier functions. The 
epidermis of newborn Mis18α-deficient mice lacked distinct stratification and 
mature hair follicles, with a reduction in the number of proliferating cells and 
increased cell death in the basal layer. Earlier expression of the Cre 
recombinase from keratin-14 promoter in the ventral region resulted in earlier 
keratinocyte death in the ventral part compared with the dorsal part in the 
absence of Mis18α, leading to more severe malformation of the ventral epidermal 
layers. As observed in Mis18α-deficient mouse keratinocytes, knockdown of Mis18α 
in HaCaT cells caused marked loss of centromeric CENP-A dots and chromosomal 
misalignment. Overall, we propose that Mis18α is important for epidermal cell 
proliferation and stratification, because it is required for the deposition of 
CENP-A at the centromeric nucleosomes.