Aberrant expression or activity of the members of the Sp/KLF family of TFs, like Sp1, Sp3 and Sp4, occurs in many human cancers [3] Sp TFs bind to GC-rich DNA elements (GC-box) in gene promoters, interact with components of the basal transcriptional machinery, cooperate with other TFs and are downstream effectors of multiple signaling pathways [3]. The gene discussed is SP3; the disease is cancer.