SPHK1 and Familial prostate cancer: Toward this end, we have reported that SK1 inhibitors [e.g., 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole, N,N-dimethylsphingosine, and FTY720] uniquely activate the ubiquitin-proteasomal degradation pathway to remove SK1 from breast and prostate cancer cells (Loveridge et al., 2010; Tonelli et al., 2010; Ohotski et al., 2012b) This remarkable property of SK1 inhibitors, which requires an initial inhibition of SK1 activity to activate the proteasome, indicates that it is possible to create cancer cells that are SK1 null, thereby eliminating its “oncogenic” effect.