Fbxo6, also called FBG2, is a component of the ubiquitin E3 ligases, which can bind high mannose N-linked glycoproteins and act as ubiquitin ligase subunits. It is involved in various biological pathways, and its dysregulation is associated with multiple diseases [1,2,3,4,5,6,7,8,9,10]. Genetic models, such as knockout (KO) and conditional knockout (CKO) mouse models, are valuable for studying its function.

In osteoarthritis (OA), FBXO6 expression decreased in cartilage samples from human OA and mouse OA models. Global or conditional knockout of FBXO6 in cartilage promoted experimental OA, as FBXO6 decreases MMP14 by ubiquitination and degradation, leading to inhibited proteolytic activation of MMP13. The TGFβ-SMAD2/3 signalling pathway regulates FBXO6 expression [1].

In influenza A virus (IAV) infection, Fbxo6-deficient mice showed decreased pulmonary viral replication, alleviated pulmonary dysfunction, and less mortality. Fbxo6 promotes proteasomal degradation of NLRX1, facilitating IAV-induced alveolar macrophages apoptosis [2].

In ovarian cancer, FBXO6 promotes K48-dependent ubiquitination and degradation of RNASET2, a tumor suppressor. High FBXO6 expression in ovarian cancer tissues is related to poor overall survival, and depletion of FBXO6 promotes cancer cell proliferation, migration, and invasion [3].

In conclusion, Fbxo6 plays essential roles in multiple biological processes and diseases. KO/CKO mouse models have revealed its functions in OA, IAV-related immune responses, and ovarian cancer development, among others. Understanding Fbxo6's functions provides potential therapeutic strategies for these diseases.