It is found in various secretions including seminal plasma, cervical mucus, and bronchial secretions, and has affinity for trypsin, leukocyte elastase, and cathepsin G. Its inhibitory effect contributes to the immune response by protecting epithelial surfaces from attack by endogenous proteolytic enzymes; the protein is also thought to have broad-spectrum antibiotic activity.

[7] The gene for SLPI is expressed by cells at many mucosal surfaces located in the tissues of the lungs, cervix, seminal vesicles, and parotid ducts.

Tissue SLPI expression reveals a clear compartmentalization, being highest in the endocervix and lowest in the endometrium of postmenopausal women.

It has been suggested that recombinant human SLPI be administered to treat symptoms of cystic fibrosis, genetic emphysema, and asthma.

This antiviral activity is due to the interference of SLPI in events that are mediated by protease, such as entry into the host cell and replication of viral genetic material.

Additionally, it has been shown that SLPI is able to bind the Annexin A2/S100A10 heterotetramer (A2t), a co-factor HIV infection, on the surface of macrophages.