Rac3, short for Ras-related C3 botulinum toxin substrate 3, is a member of the Rho family small guanosine triphosphatases (GTPases). It is crucial in regulating the cytoskeleton, playing significant roles in cellular and developmental biology, as well as in pathological processes such as neurodevelopmental disorders and cancer [1].

In mouse models, Rac1 and Rac3 double knockout (Rac1/Rac3-DKO) mice under the control of the Atoh1 promoter showed normal cochlear hair cell (HC) morphology at 13 weeks and normal hearing function at 24 weeks, indicating that Rac3 is dispensable for the maturation of cochlear HCs in the post-mitotic state or for hearing maintenance following HC maturation [5]. In bladder cancer, knockdown of Rac3 inhibited cell proliferation, migration, and invasion, and caused cell cycle arrest. It activated PI3K/AKT/mTOR-mediated autophagy, suggesting a potential therapeutic strategy by targeting Rac3 and autophagy simultaneously [2]. In endometrial cancer, Rac3 promoted cell proliferation and invasion by increasing fatty acid synthase (FASN) expression, and its high expression was correlated with poor prognosis [4]. Also, in endothelial cells, Rac3 promoted ox-LDL induced endothelial dysfunction by down-regulating autophagy [3].

In conclusion, Rac3 is involved in various biological processes and disease conditions. Mouse knockout models have been valuable in revealing its dispensable role in cochlear HC maturation and hearing maintenance. In cancer, such as bladder and endometrial cancer, Rac3 promotes tumor progression, highlighting its potential as a therapeutic target. Its role in endothelial cell dysfunction also indicates its importance in atherosclerosis-related pathologies.