[9] Due to the large size of the death domain family protein superfamily, some death domain proteins may have a role to play in cancer and many other infections through several families of DD-proteins and specific gene alterations that have a downstream function to induce cell apoptosis.

Many of these alterations occur in genes encoding mediators of apoptosis or necroptosis, potentially enabling the development of resistance to cell death, an important hallmark of cancer.

Many of these malignancies have a subset of cases harboring genomic alterations in components of intrinsic or extrinsic cell death pathways, including amplification and overexpression of the Fas-associated via death domain (FADD) and inhibitor of apoptosis proteins (IAP), as well as mutations in caspase-encoding genes.

Notably, the Fas death domain can have mutations that lead to autoimmune lymphoproliferative syndrome (ALPS), lung cancer, and squamous cell carcinoma.

Notably, a two-point mutation that occurs at the A1009G and E256G sites can cause a defect in apoptotic pathways in people who have ALPS (Peters, 1999).