Recent studies in melanoma have indicated that some components of the PI3K pathway (PTEN, MTOR, IRS4, PIK3R1, PIK3R4, PIK3R5 and NFKB1) are co-mutated in 17% of BRAF V600E mutant and 9% of NRAS mutant melanomas [5]. The gene discussed is IRS4; the disease is melanoma.