Rabinovich et al.55 reported that downregulation of ASS1, an enzyme directly upstream of ASL, increased pyrimidine synthesis and cancer cell proliferation but did not see the same connection with ASL. The different effect of siRNA knockdown of ASL and ASS1 on D492 and D492M survival reported here support a mutually exclusive relationship of ASL and ASS1 as only ASL and not ASS1 was found to be essential for growth of D492M (Fig. 5c and Supplementary figure 3). Here, ASS1 is linked to cancer.