An enzyme that breaks down peptides by cutting their amino acid chains—the main reason most peptides have short half-lives.Peptidases (proteases) cleave peptide bonds through hydrolysis. They are classified as endopeptidases (cleave internal bonds) or exopeptidases (remove terminal residues). Key peptidases affecting therapeutic peptides include DPP-IV (cleaves N-terminal dipeptides from GLP-1, GIP), NEP/CD10 (degrades natriuretic peptides, VIP, substance P), ACE (cleaves angiotensin I, bradykinin), and aminopeptidases (degrade N-terminal residues). Peptide drug design frequently incorporates modifications—D-amino acids, cyclization, PEGylation—specifically to resist peptidase degradation.