The E3 ubiquitin ligase responsible for Rac1 degradation, the tumor suppressor HACE1 (HECT Domain and Ankyrin Repeat Containing E3 Ubiquitin Protein Ligase 1), is prominently down-regulated or mutated in various cancers, leading to enhanced Rac1 signaling, that ultimately correlates with disease progression (Zhao et al., 2013; Cook et al., 2014; Li et al., 2019). The gene discussed is HACE1; the disease is cancer.