RGCC, also known as regulator of cell cycle or response gene to complement 32 protein, is involved in multiple biological processes. It plays a role in cell cycle regulation, and is associated with pathways related to metabolism, fibrosis, and neural development. Genetic models, such as KO mouse models, are valuable for studying its functions, as they can help reveal its role in specific biological processes and disease conditions [1-4].

In triple-negative breast cancer (TNBC), RGCC is aberrantly upregulated in pulmonary metastatic cells. It promotes the kinase activity of PLK1, which phosphorylates AMPKα2, facilitating TNBC lung metastasis by increasing oxidative phosphorylation and fatty acid oxidation [1].

In pulmonary fibrosis, RGCC levels decrease, and overexpression of RGCC in lung fibroblasts attenuates the effects of TGF-β on collagen levels. Mice with constitutive RGCC gene deletion accumulate more collagen in their lungs in response to bleomycin [2].

In neocortical development, RGCC deficiency hampers normal cell cycle process and dysregulates the mitotic spindle, leading to abnormal NSC differentiation and brain malformation [3].

In medaka spermatogonia, Smo mediates spermatogonia proliferation through Gli1-Rgcc-Cdk1 axis, and Rgcc overexpression rescues cell apoptosis caused by Smo or Gli1 inhibition [4].

In conclusion, RGCC is essential for maintaining normal cell cycle, metabolism, and tissue homeostasis. KO/CKO mouse models have contributed to understanding its role in diseases like TNBC lung metastasis and pulmonary fibrosis. These findings suggest that targeting RGCC could potentially be a therapeutic strategy for these diseases.