Are abundant, highly conserved adaptor proteins of ~30 kDa found in all eukaryotes. Similar to the binding of SH2 domains to phosphorylated tyrosine residues, 14-3-3 proteins usually bind to their client protein via a phosphorylated Ser- or Thr-residue in a sequence-specific context (mode I: RSXpS/TP; mode II: RXXXpS/TXP with p indicating the phosphorylated residue and X any amino acid). 14-3-3 proteins assist in the stabilization of the client protein in either an active or inactive conformation. 14-3-3 proteins regulate a multitude of biological processes ranging from metabolic control to the regulation of apoptosis, cell cycle progression, and mitogenic signaling. One of the seven human 14-3-3 genes, 14-3-3σ/stratifin, is frequently epigenetically silenced in breast, lung, and prostate cancer and is discussed as a tumor suppressor gene.