Whilst a twofold modulation of kinase activity may seem modest, it is important to remember that even a 50 % increase in expression and activity of the closely related DYRK1A has profound physiological effects in mice and phenocopies some Down’s syndrome defects [11, 15] whilst a 50 % decrease in DYRK1A causes even more dramatic effects in Drosophila, mice and human patients including microcephaly, growth retardation and behavioural defects [11, 50, 51]. The gene discussed is DYRK1A; the disease is microcephaly.