Ruvbl2, also known as Reptin, is a highly conserved AAA+ ATPase. It forms a hetero-hexameric complex with Ruvbl1 and participates in diverse cellular processes, including chromatin remodeling, transcription, and the assembly of large macromolecular complexes [1]. It is associated with pathways like nonsense-mediated mRNA decay, Fanconi Anemia, and is crucial for normal cellular function and development. Genetic models are valuable for studying its function.

In zebrafish, a loss-of-function allele of ruvbl2 (ruvbl2Δ) led to ventricular hyperplasia, demonstrating that Ruvbl2 represses cardiomyocyte proliferation during heart development and regeneration [2]. In mice, knockout of PVH RUVBL2 resulted in hyperphagic obesity, indicating its role in appetite control through enhancing excitatory synaptic transmission in the hypothalamus [3]. In hepatocellular carcinoma, high levels of RUVBL2, regulated at genomic, epigenetic, and transcriptional levels, were associated with poor prognosis, and its overexpression promoted carcinogenesis through the HSP90-CDC37, AKT, and ERK/MAPK pathways [4].

In conclusion, Ruvbl2 is essential for multiple biological processes. Studies using gene knockout models in zebrafish and mice have revealed its role in heart development, appetite regulation, and cancer-related processes. These findings highlight the significance of Ruvbl2 in understanding normal physiological functions and disease mechanisms, potentially guiding the development of therapeutic strategies for related diseases.