Riok1, or RIO Kinase 1, is involved in various biological processes and pathologies, especially cancer-related pathways. It has been implicated in multiple cellular functions, potentially through its interaction with other proteins and regulation of key signaling pathways. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, would be valuable to further elucidate its functions [1-10].

In colorectal cancer, blocking Riok1 using a pharmacological inhibitor or knockdown decreased radioresistance both in vitro and in vivo. Riok1 was found to regulate radioresistance by suppressing the p53 signaling pathway through phosphorylating G3BP2 at Thr226, which facilitated p53 ubiquitination by MDM2 [1]. In epithelial ovarian cancer, disruption of the SPC25/Riok1/MYH9 axis using a competitive inhibitory peptide attenuated cancer stem cell phenotypes and enhanced platinum efficacy, suggesting its role in maintaining tumor stemness and platinum resistance [2]. In non-small cell lung cancer, knockdown of Riok1 inhibited cell proliferation, migration, invasion, and tumorigenesis, and increased apoptosis when treated with cisplatin [3]. In glioma, silencing Riok1 inhibited the proliferation, migration, and invasion of glioma cell lines by suppressing AKT and c-Myc expression [4]. In podocytes, soluble RARRES1 interacted with and inhibited Riok1, leading to p53 activation and apoptosis, promoting glomerular disease progression [5].

In conclusion, Riok1 plays crucial roles in cancer development, radioresistance, tumor stemness, and drug resistance in various cancers, as well as in glomerular disease progression. Studies using KO/CKO mouse models would likely further clarify its functions in these disease areas, helping to understand the underlying mechanisms and potentially providing new therapeutic targets.