Myo9b, a myosin protein, is both an actin-based motor and a Rho GTPase-activating protein (GAP) [2,3,5,6,7]. As a RhoGAP, it negatively regulates Rho activity, which is crucial for coordinating the organization and dynamics of the actin cytoskeleton, a key process in many cellular functions such as cell motility, migration, and morphogenesis [2,3,5]. It is involved in multiple biological pathways related to cell movement and tissue development. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying Myo9b's functions.

In Myo9b-deficient leukocytes, cell migration is impaired due to increased Rho activity, suggesting Myo9b's role in regulating cell motility through local inhibition of Rho activity [2]. Myo9b-deficient mice show a high incidence of microphthalmia, cataracts, and disordered lens vesicle formation during embryonic development, indicating its importance in ocular lens pit morphogenesis [3]. Myo9b-null mice also have degenerating axons in sciatic and optic nerves, linking it to peripheral and central nervous system axon maintenance and suggesting its association with Charcot-Marie-Tooth disease type 2 neuropathies and isolated optic atrophy [4]. In addition, Myo9b-deficient osteocytic cells have abnormal responses to mechanical stimuli, demonstrating its role in bone cell responses to mechanical stress [6].

In conclusion, Myo9b is essential for regulating cell motility, tissue morphogenesis, and the function of nerve and bone cells. KO mouse models have been vital in uncovering Myo9b's roles in diseases such as eye malformations, neuropathies, and potentially autoimmune diabetes, inflammatory bowel disease, coronary artery disease, and esophageal adenocarcinoma [1,4,8,9,10]. These findings enhance our understanding of the biological processes and disease mechanisms associated with Myo9b.