IL-32 is a proinflammatory cytokine with both extracellular and intracellular functions. IL-32 was originally identified as a natural killer transcript 4 (NK4). Several isoforms of IL-32 have been identified, and IL-32α is the most abundant. Overexpression of IL-32α in myeloid cell lines enhances natural killer cell-mediated killing, and IL-32 expression can be induced by IL-18 in NK cells. IL-32α can be released by some epithelial cell lines in response to INF-γ, TNF-α, and IL-1β. IL-32 can induce production of various cytokines including TNF-α, IL-1β, IL-8 and IL-6 through NF-κB and p38 MAPK activation. IL-32 works synergistically with IL-17 to induce osteoclast differentiation. Recombinant IL-32α can induce macrophage apoptosis in the presence of M. tuberculosis. Intracellular IL-32α increases IL-6 production by interacting with PKCε and STAT3, which not only increases STAT3 phosphorylation but also enhances STAT3 recruitment to the IL-6 promoter. IL-32 can synergize with NOD1 and NOD2 ligands to induce IL-1β and IL-6 through the caspase I-dependent pathway. IL-32 has been associated with pathogenesis of many chronic inflammatory diseases including rheumatoid arthritis and ulcerative colitis. IL-32 is highly expressed in various cancers including gastric and pancreatic cancer. Studies have suggested that IL-32 can function as an angiogenic factor. In addition, IL-32α expression in liver cells is increased following progression of many liver diseases. Also, IL-32 is involved in the immune response to many viruses including HIV, influenza A, hepatitis B, and papillomavirus.