In this study, we provide evidence for the novel observations that this interactome is endogenously upregulated in DTX-resistant PCa cells; that LEDGF/p75 interacts as part of an endogenous nuclear complex with JPO2, c-MYC, menin, MLL, ASK, PogZ, IWS1, HRP2, and H3K36me2 in DTX-resistant PCa cells; and that depletion of selected members of this interactome decreases the survival, clonogenicity, and tumorsphere formation capacity of DTX-resistant PCa cells. Here, POGZ is linked to posterior cortical atrophy.