Kcmf1, or Potassium channel modulatory factor 1, is an E3 ubiquitin ligase. It has been linked to multiple biological processes, including renal tubulogenesis, preeclampsia, and tumor development in mammals [1,2,4,5,6]. It forms a ubiquitin ligase complex with proteins like UBA6, BIRC6, and UBR4, which is involved in regulating the integrated stress response (ISR) in certain epithelial tumors [3]. It also participates in the RAD6-KCMF1-UBR4-mediated regulation of autophagy, and its associated ubiquitin ligase system may be a potential therapeutic target in renal cell carcinoma (RCC) [2,4].

In mud crabs, knockdown of KCMF1-like (a homolog) led to an increase in white spot syndrome virus (WSSV) copy number and impairment of hemocyte apoptosis rate, indicating its role in antiviral defense [1]. In pancreatic cancer, Kcmf1-knockdown gene trap mice showed a reduced number and size of premalignant lesions and absence of pancreatic cancer formation, suggesting its pro-oncogenic functions [6].

In summary, Kcmf1 plays essential roles in multiple biological processes and diseases. Gene-knockdown models in invertebrates and mice have revealed its significance in antiviral immunity and tumor development, providing potential targets for therapeutic interventions in related disease areas.