An elegant in-depth mechanistic analysis of CHD4, using cancer-associated missense mutations transposed into the Drosophila homologue Mi-2, revealed heterogeneous defects (i.e., reduction in protein stability, disruption of DNA binding, and loss of ATPase activity or coupling), leading mainly to loss-of-function [258], nicely supported by structural work [72]. The gene discussed is DNAH8; the disease is cancer.