Rala, a member of the small GTPase Ras superfamily, acts as a molecular switch toggling between inactive GDP-bound and active GTP-bound states. It is involved in diverse cellular functions such as vesicle trafficking, filopodia formation, mitochondrial fission, and cytokinesis [3]. It participates in multiple pathways like those related to exocytosis through interacting with the exocyst complex [5]. Rala is of great biological importance as it is associated with various physiological and pathological processes. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In white adipocytes, deletion of Rala in mice prevents mitochondrial fragmentation caused by high-fat diet (HFD), reduces HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, Rala increases mitochondrial fission by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1 [1]. In breast cancer, inhibition of RalA-GTP form attenuates the interaction between ANXA2 and Src, which is part of a complex promoting CTC formation and metastasis [2]. In osteosarcoma, knocking down Rala could potentially impact tumor cell proliferation, migration, and invasion as it is highly expressed in human osteosarcoma tissues and cell lines [4].

In conclusion, Rala plays essential roles in multiple biological processes. Studies using KO/CKO mouse models have revealed its significance in obesity-related metabolic dysfunction, breast cancer metastasis, and osteosarcoma development. Understanding Rala's functions can provide new insights into these disease mechanisms and potentially lead to novel therapeutic strategies.