F-box protein 48 (FBXO48)

FBXO48 is a member of the F-box protein family and functions as an E3 ubiquitin ligase subunit within the SCF complex. Its primary known role is to recognize and target phosphorylated AMPKα for polyubiquitylation and subsequent proteasomal degradation. This positions FBXO48 as a negative regulator of cellular energy homeostasis, controlling the cellular signaling cascade that governs mitochondrial fission, autophagy, and insulin sensitivity. Inhibition of FBXO48, for example with small molecules such as BC1618, can prevent pAMPKα degradation, enhance AMPK-mediated metabolic effects, and improve hepatic insulin sensitivity, suggesting promise for metabolic disease therapy. FBXO48 is genomically localized to 2p13.3, a region connected to Parkinson's disease in genetic studies, though direct disease–causing mutations have not been established.

Other names

F-box only protein 48FBXO48FBX48F-box protein 48

Inhibition of FBXO48 prevents ubiquitylation and degradation of pAMPKα, resulting in maintained AMPK signaling and downstream metabolic effects