We recently identified Protein kinase N1 (PKN1) as a negative regulator of neuronal AKT activity during postnatal cerebral development. Given the pivotal role of the AKT pro-survival signalling cascade in ischemia/reperfusion, our investigation aimed to determine whether PKN1-mediated AKT inhibition remains relevant during pathological conditions in the mature brain. Employing adult wild type and global Pkn1 knockout (Pkn1-/-) mice, we observed that Pkn1 knockout indeed imparts a protective phenotype in both, in vitro and in vivo stroke models. However, this was not associated with enhanced AKT activity. Instead, bulk RNA sequencing data from post-ischemic in vitro brain tissue indicated changes in the regulation of energy metabolism upon Pkn1 knockout. We next conducted a comprehensive assessment of the metabolic phenotype of Pkn1-/- brain tissue, utilizing stable isotope tracing, metabolomic analysis and real-time seahorse measurements of glycolytic and oxygen consumption rates. Intriguingly we found that Pkn1-/- brain tissue exhibited a strongly altered energy metabolism, which was also associated with the protective phenotype in in vitro stroke models. We further provide mechanistic insights by identifying several metabolic enzymes as substrates of PKN1. In summary, our findings reveal a novel regulatory role of PKN1 in cerebral energy metabolism and uncover its impact on post-ischemic neuroprotection and neurodegeneration. This underscores the multifaceted role of PKN1 in the brain, spanning from a developmental gatekeeper of AKT to a novel regulator of cerebral energy homeostasis.