ADAM family proteins are membrane proteins that were first shown to function in sperm-egg fusion. Each contains a disintegrin domain and a metalloproteinase domain (though not all are catalytically active), and they are important regulators of cell adhesion and recognition - for example, in muscle and brain development. Ulrike Novak and colleagues have been studying how ADAM22, a catalytically inactive ADAM expressed in the brain, reaches the cell surface. On p. 3296, they report that the cytoplasmic domain of ADAM22 interacts with 14-3-3 proteins. These proteins regulate many important cellular processes - usually by binding to phosphorylated residues in their target. The authors show that brain-expressed 14-3-3 proteins interact preferentially with the phosphorylated precursor form of ADAM22, mainly through the first of two 14-3-3-binding sites in its cytoplasmic tail; ADAM22 mutants that lack these binding sites fail to accumulate normally at the cell surface unless an ER-retention motif is also deleted. Thus, 14-3-3 proteins might help to transport ADAM22 to the cell membrane by masking ER-retention signals - a novel role for this family.