Kcmf1, or Potassium channel modulatory factor 1, is an E3 ubiquitin ligase. It plays a vital role in multiple biological processes, including renal tubulogenesis, preeclampsia, and tumor development in mammals. It is involved in ubiquitination-related pathways, which are crucial for protein degradation and regulation of various cellular functions [1,2,3,4,5].

In invertebrates like the mud crab (Scylla paramamosain), KCMF1-like was identified. RNA interference (RNAi) experiments, a form of in-vivo loss-of-function study, showed that knockdown of KCMF1-like increased the white spot syndrome virus (WSSV) copy number and impaired hemocytes apoptosis rate, indicating its role in defense against virus infection in the mud crab [1]. In patients with renal cell carcinoma (RCC), disruption in the networking of KCMF1-linked ubiquitin ligase impairs autophagy in CD8+ memory T cells, suggesting its potential as a therapeutic target [2]. Also, in a subset of epithelial tumors, a ubiquitin ligase complex containing Kcmf1 is required for survival, and suppressing related components can lead to tumor regression [3].

In conclusion, Kcmf1 is essential in various biological processes, especially those related to ubiquitination-mediated protein regulation. Studies using loss-of-function models, such as RNAi in invertebrates and disruption of its associated ligase in human diseases, have revealed its importance in antiviral defense in invertebrates and in tumor-related processes in mammals, highlighting its potential as a therapeutic target in cancer.