[1] Discovered by Gopal Chunder Roy in 1873, the first cysteine protease to be isolated and characterized was papain, obtained from Carica papaya.

The first step in the reaction mechanism by which cysteine proteases catalyze the hydrolysis of peptide bonds is deprotonation of a thiol in the enzyme's active site by an adjacent amino acid with a basic side chain, usually a histidine residue.

The thioester bond is subsequently hydrolyzed to generate a carboxylic acid moiety on the remaining substrate fragment, while regenerating the free enzyme.

The ability of macrophages and other cells to mobilize elastolytic cysteine proteases to their surfaces under specialized conditions may also lead to accelerated collagen and elastin degradation at sites of inflammation in diseases such as atherosclerosis and emphysema.

[9] Successful results have been reported against nematodes such as Heligmosomoides bakeri, Trichinella spiralis, Nippostrongylus brasiliensis, Trichuris muris, and Ancylostoma ceylanicum; the tapeworm Rodentolepis microstoma, and the porcine acanthocephalan parasite Macracanthorhynchus hirundinaceus.

They provide an alternative mechanism of action to current anthelmintics and the development of resistance is thought to be unlikely because it would require a complete change of structure of the helminth cuticle.

In several traditional medicines, the fruits or latex of the papaya, pineapple and fig are widely used for treatment of intestinal worm infections both in humans and livestock.