The family of proteins and natural peptides containing γ-carboxyglutamic acid (Gla) residues has a limited number of members found in such diverse sources as blood plasma, bone tissue, and snail venoms. The best characterized subfamily consists of the so-called vitamin K-dependent plasma proteins found in the blood and is the topic of this chapter. In the conversion of glutamate to Gla, an extra carboxyl group is added post-translationally to the γ-carbon of a restricted number of glutamate residues in the amino-terminal Gla domain, which received its name from this unusual residue, by a vitamin K-dependent carboxylase (1). The carboxylase binds primarily to a propeptide that is cleaved off before secretion of the proteins, but the signal that limits the carboxylation to glutamate residues within the first 40 amino acid residues has not been identified. The Gla-containing plasma proteins have 9-12 Gla residues depending on how many Glu residues are encoded by the two exons covering the first approx 46 residues of the proteins because all Glu residues in this part of the protein become γ-carboxylated. The resulting dicarboxylic Gla residues have significantly higher affinity for Ca²⁺, compared to the precursor Glu residues, and this ability to chelate Ca²⁺ions under physiological conditions ([Ca²⁺]_free = 1-1.5 mM in the blood) is pivotal for biological activity.