APPL1 and nervous system disorder: Conversely, decrease of Htt to 50% of wild type levels leads to de-repression of Abl kinase activity, which in turn compensates for its sub-optimal level of activation in the absence of Appl. This unexpected apparent balance of activation and inhibition of Abl by Appl and htt, whose mutant orthologs are central players in human neurological disease, may define a conserved functional interaction to maintain Abl activity in the relatively narrow window to appropriately effect axon outgrowth.