SKIII (SphK-I2) is a selective inhibitor of sphingosine kinase 1 (SphK1), an enzyme involved in the metabolism of sphingolipids and the production of sphingosine-1-phosphate (S1P). By inhibiting SphK1, SKIII disrupts the S1P signaling pathway, which plays a key role in cell proliferation, survival, migration, and inflammation. One major application of SKIII is in cancer research. It has been used to induce apoptosis in various cancer cell lines, including leukemia, breast cancer, and glioblastoma, by shifting the balance toward pro-apoptotic ceramide accumulation and reducing pro-survival S1P levels. This makes SKIII a valuable tool for studying tumor growth mechanisms and evaluating potential therapeutic strategies. SKIII is also used to investigate inflammatory processes and immune responses, as S1P is involved in immune cell trafficking and cytokine production. In models of autoimmune and inflammatory diseases, SKIII helps elucidate the role of SphK1 in disease progression. Additionally, SKIII serves as a pharmacological tool in neuroscience research, where sphingolipid signaling affects neuronal survival and neurodegeneration. Its ability to cross cell membranes makes it suitable for both in vitro and in vivo studies. Overall, SKIII is widely applied in biomedical research to probe sphingolipid-mediated pathways and assess the therapeutic potential of targeting SphK1 in cancer, inflammation, and neurological disorders.