F-box and leucine-rich repeat protein 5 (FBXL5)

F-box and leucine-rich repeat protein 5 (FBXL5) is a member of the F-box protein family, characterized by the F-box motif and multiple leucine-rich repeats[1]. It acts as a substrate recognition component of the SCF-type E3 ubiquitin ligase complex, playing a critical role in the selective degradation of proteins via ubiquitination: most notably, by promoting iron homeostasis through oxygen- and iron-dependent degradation of iron regulatory protein 2 (IRP2)[1][2][3][4]. The protein uses a unique hemerythrin-like domain to sense intracellular iron and oxygen levels, regulating its stability and substrate targeting based on these conditions[2]. FBXL5 also mediates the proteasomal degradation of additional proteins such as DCTN1, SNAI1, NABP2, and CITED2, implicating it in processes including cell cycle regulation, DNA damage response, oxidative stress, and stem cell maintenance[1][3]. Downregulation or genetic disruption of FBXL5 is associated with disorders ranging from iron overload syndromes and neurodegeneration to hematopoietic failure and cancer, chiefly through its impact on iron homeostasis and reactive oxygen species signaling[3]. Currently, there are no known interacting drugs that specifically target FBXL5, but it represents a potentially valuable therapeutic target for diseases linked to iron metabolism and oxidative damage[3][1].

Other names

FBXL5F-box/LRR-repeat protein 5FBL4FBL5FLR1F-box protein FBL4/FBL5p45SKP2-like protein

Drugs or compounds targeting FBXL5 would likely modulate its E3 ubiquitin ligase activity, affecting degradation of substrates such as IRP2, DCTN1, SNAI1, CITED2, and NABP2[1][3]. Potential mechanism: restoration of iron homeostasis via FBXL5-mediated IRP2 degradation[3].