α-Amidation is a critical post-translational processing of many bioactive peptides in the nervous and endocrine systems. PAM, a bifunctional enzyme, with two catalytic domains PHM and PAL, catalyzes the sequential two-step conversion of glycine-extended peptides into COOH-terminal amidated peptides. Alternative splicing and tissue specific processing generate multiple forms of PAM. As a rate-limiting enzyme in biosynthetic pathway of peptides, levels of PAM are tissue specific and under the regulation of hormones and developmental cues.