Elevated amounts of 14-3-3 protein in cerebrospinal fluid are usually a sign of rapid neurodegeneration; a common indicator of Creutzfeldt–Jakob disease.

These proteins contain a number of known common modification domains, including regions for divalent cation interaction, phosphorylation & acetylation, and proteolytic cleavage, among others established and predicted.

There are common recognition motifs for 14-3-3 proteins that contain a phosphorylated serine or threonine residue, although binding to non-phosphorylated ligands has also been reported.

In bovine brain samples, 14-3-3 proteins were located in the 14th fraction eluting from a DEAE-cellulose column and in position 3.3 on a starch electrophoresis gel.

Binding of 14-3-3 has little effect on Cdc25C activity, and it is believed that 14-3-3 regulates Cdc25C by sequestering it to the cytoplasm, thereby preventing the interactions with CycB-Cdk1 that are localized to the nucleus at the G2/M transition.

[citation needed] The presence of large gene families of 14-3-3 proteins in the Viridiplantae kingdom reflects their essential role in plant physiology.