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 are valuable for studying its functions, as they can help uncover its roles in different biological contexts.

In triple-negative breast cancer (TNBC), RGCC is aberrantly upregulated in pulmonary metastatic cells. It activates PLK1 kinase activity, which phosphorylates AMPKα2. This leads to increased oxidative phosphorylation and fatty acid oxidation, supporting TNBC cell survival and colonization during lung metastasis [1].

In pulmonary fibrosis, contrary to previous beliefs, RGCC has a protective role. Its levels decrease in fibrotic lungs, and overexpression in lung fibroblasts attenuates TGF-β-induced collagen accumulation. Mice with RGCC gene deletion accumulate more collagen in response to bleomycin [2].

In neocortical development, RGCC deficiency in mice hampers normal cell cycle and spindle orientation, diminishing the neural stem cell (NSC) pool and causing NSC pre-differentiation and brain malformation [3].

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

In conclusion, RGCC is essential for maintaining normal cell cycle processes, metabolism, and tissue homeostasis. Studies using gene-knockout mouse models have revealed its significance in diseases like TNBC lung metastasis, pulmonary fibrosis, and in normal biological processes such as neural development and spermatogonia proliferation. Understanding RGCC provides potential therapeutic targets for related diseases.