Variation in catalytic site and putative G-loop sequences may account for the large differences in intrinsic in vitro kinase activity between the isoforms (PI5P4Kα being the most active isoform).10 The PI5P4Ks have established links to cancer,9,11 specific associations suggest that inhibition of PI5P4Kα may be beneficial in p53 mutant breast cancer12,13 and acute myeloid leukaemia14 where PIP4K2A has been identified as a cytogenetic risk factor.15,16 This association potentially reflects the role of PI5P4Kα in cell proliferation and the higher levels of expression in hematopoietic cells.17 This evidence concerns the gene TP53 and cancer.