The productive replication of HIV 1 requires intricate interactions between viral proteins and host cell machinery. However, the contributions of lysosomal functions for HIV 1 replication are not fully understood. RCMI researchers have made a novel discovery that treating cells with pharmacological agents known to inhibit lysosomal functions interfere with HIV 1 replication. This reveals that lysosomal functions are involved in regulating the HIV 1 life cycle. Among the compounds tested, bafilomycin A1 exerted a potent inhibition of HIV 1 replication. Bafilomycin A1 appears to inhibit HIV 1 replication at the step after the cell entry, reverse transcription, and viral integration. The research team further demonstrated that bafilomycin A1 treatment leads to cellular changes including the lysosomal cholesterol accumulation and alterations in lysosome positioning. This discovery not only suggests an interplay between lysosomal functions and HIV 1 replication but also opens up the lysosomal pathway as a new target for developing novel therapeutic approaches for HIV/AIDS.