A screen of compounds capable of inhibiting binding between HOIL-1L NZF and linear ubiquitin chains identified a small compound that inhibited SHARPIN NZF as well as HOIL-1L NZF binding to linear ubiquitin chains, supporting the synergistic effect of the two NZF domains on cell death protection and suggesting a potential therapeutic strategy for targeting increased LUBAC activity in diseases such as cancer. The gene discussed is SHARPIN; the disease is cancer.