The CNS penetrant, pan-PI3K/Akt/mTOR (p110α, p110β, p110δ, and p110γ) inhibitor paxalisib (formerly GDC-0084), was developed for the treatment of glioblastoma, as approximately 80% of cases harbor recurring mutations/amplification in genes mapping to the PI3K signaling axis (17). The gene discussed is PIK3CD; the disease is glioblastoma.