Fem1b, or Fem1 homolog B, acts as a substrate recognition subunit for CULLIN 2-based E3 ubiquitin ligase complexes. It plays a crucial role in the ubiquitin-proteasome system, determining the specificity of protein degradation [2,4,5,7]. It is involved in several biological processes, such as redox regulation by controlling mitochondrial activity, and has been associated with pathways related to oxidative stress and angiogenesis [1,3,6].

In a study, the release of a FEM1b-FNIP1 axis inhibitor from a hydrogel ameliorated oxidative stress and stimulated angiogenesis, promoting diabetic wound healing, suggesting its significance in diabetic wound repair [1]. Also, FEM1B recognizes C-degrons containing a C-terminal proline, and its dimerization state and interaction with degrons are important for CRL2FEM1B-mediated polyubiquitination and protein turnover [2]. Additionally, during reductive stress, CUL2FEM1B selectively recruits reduced FNIP1, regulated by BEX family pseudosubstrate inhibitors, and FEM1B gain-of-function mutation leads to developmental syndromes, indicating its role in maintaining cellular and organismal homeostasis [3]. Moreover, a recurrent de novo missense variant in FEM1B in humans causes a severe neurodevelopmental disorder with behavioral phenotypes and malformations, and overexpression of this variant in mouse brain development results in delayed neuronal migration and signs of oxidative stress in cells [7].

In conclusion, Fem1b is essential in the ubiquitin-proteasome system, redox regulation, and maintaining cellular homeostasis. Studies related to Fem1b, including those using models, have revealed its significance in processes like diabetic wound healing and neurodevelopmental disorders, highlighting its potential as a therapeutic target for related diseases.