As the key components of innate immunity, human host defense antimicrobial 
peptides and proteins (AMPs) play a critical role in warding off invading 
microbial pathogens. In addition, AMPs can possess other biological functions 
such as apoptosis, wound healing, and immune modulation. This article provides 
an overview on the identification, activity, 3D structure, and mechanism of 
action of human AMPs selected from the antimicrobial peptide database. Over 100 
such peptides have been identified from a variety of tissues and epithelial 
surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary 
systems. These peptides vary from 10 to 150 amino acids with a net charge 
between -3 and +20 and a hydrophobic content below 60%. The sequence diversity 
enables human AMPs to adopt various 3D structures and to attack pathogens by 
different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial 
surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are 
able to block cell wall biosynthesis by binding to lipid II. Lysozyme is 
well-characterized to cleave bacterial cell wall polysaccharides but can also 
kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the 
long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding 
and disrupting the curved anionic bacterial membrane surfaces by forming pores 
or via the carpet model. Furthermore, dermcidin may serve as ion channel by 
forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα 
can initially recognize bacterial peptidoglycans followed by pore formation in 
the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to 
exert their effects. It appears that granulysin enters cells and kills 
intracellular pathogens with the aid of pore-forming perforin. This arsenal of 
human defense proteins not only keeps us healthy but also inspires the 
development of a new generation of personalized medicine to combat 
drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, 
multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, 
isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able 
to induce the expression of antimicrobial peptides, opening new avenues to the 
development of anti-infectious drugs.