Much of the understanding about how the IRS proteins impact tumor cell functions has come from studies of cell lines in which IRS expression has been stably knocked down by shRNA or knocked out by Cre/lox recombination or CRISPR/Cas9 mediated gene targeting and restoration of exogenously expressed WT and mutant proteins (1, 10, 11, 12). The gene discussed is IARS1; the disease is neoplasm.