Mutations in SF3B1, SRSF2, and U2AF1 are uniformly heterozygous and mutually exclusive (Yoshida et al., 2011), findings which have led to the hypothesis that the remaining wild-type allele is essential for cells with splicing factor mutations and fueled efforts to target spliceosome function in patients with splicing factor-mutant myeloid malignancies (Lee et al., 2016; Fong et al., 2019). The gene discussed is U2AF1; the disease is myeloid neoplasm.