JARID1B’s demethylase-independent functions are largely unexplored in cancer but are predictable from studies of Lid, the single JARID1 family homologue in D. melanogaster. Lid’s catalytically inactive form rescues the embryonic lethality of its deletion mutant [67] and promotes transcription by diverse mechanisms [68–70]. The gene discussed is KDM5B; the disease is cancer.