Inheritance of genetic material requires that chromosomes segregate faithfully 
during cell division. Failure in this process can drive to aneuploidy 
phenomenon. Kinetochores are unique centromere macromolecular protein structures 
that attach chromosomes to the spindle for a proper movement and segregation. A 
unique type of nucleosomes of centromeric chromatin provides the base for 
kinetochore formation. A specific histone H3 variant, CENPA, replaces 
conventional histone H3 and together with centromere-specific-DNA-binding 
factors directs the assembly of active kinetochores. Recent studies on CENPA 
nucleosomal structure, epigenetic inheritance of centromeric chromatin and 
transcription of pericentric heterochromatin provide new clues to our 
understanding of centromere structure and function. This review highlights the 
role and dynamics of CENPA assembly into centromeres and the potential 
contribution of this kinetochore protein to autoimmune and cancer diseases in 
humans.