We show that (i) PIP4K2A expression is enhanced in PCa with AR signaling reflecting CRPC, (ii) PI5P4Kα localizes to the lysosome where its influence on mTORC1 signaling may affect AR, and (iii) inhibiting PI5P4Kα exposes PCa cells to a metabolic vulnerability that may enhance efficacy of targeted therapeutics. Here, AR is linked to posterior cortical atrophy.