Dysregulation of kinase functions drive many cancers, as well as other diseases including Parkinson’s, making them highly desirable therapeutic targets for drug development. However, many kinases have pleiotropic functions, so that even conventional competitive inhibitors with high on-target specificity/selectivity can lead to dose-limiting side effects that constrain their success in the clinic. Many human kinases are activated by specific phosphorylation, which often act as ‘on off’ switches. However, most kinases are also phosphorylated on multiple amino acids throughout the length of the protein, the function of which are little unknown. In this talk, I will elaborate on how understanding the nuances in regulation of kinase functions, using PKCδ as an example, can reveal new opportunities for maximising on-cancer targeting effects while minimising off-cancer effects.