Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2 (PubMed:19762596, PubMed:19762597). The C-terminal domain of FBXL5 contains a redox-sensitive [2Fe-2S] cluster that, upon oxidation, promotes binding to IRP2 to effect its oxygen-dependent degradation (PubMed:32126207). Under iron deficiency conditions, the N-terminal hemerythrin-like (Hr) region, which contains a diiron metal center, cannot bind iron and undergoes conformational changes that destabilize the FBXL5 protein and cause its ubiquitination and degradation (PubMed:19762596, PubMed:19762597). When intracellular iron levels start rising, the Hr region is stabilized (PubMed:19762596, PubMed:19762597). Additional increases in iron levels facilitate the assembly and incorporation of a redox active [2Fe-2S] cluster in the C- terminal domain (PubMed:32126207). Only when oxygen level is high enough to maintain the cluster in its oxidized state can FBXL5 recruit IRP2 as a substrate for polyubiquitination and degradation (PubMed:32126207). Promotes ubiquitination and subsequent degradation of the dynactin complex component DCTN1 (PubMed:17532294). Within the nucleus, promotes the ubiquitination of SNAI1; preventing its interaction with DNA and promoting its degradation (PubMed:24157836). Negatively regulates DNA damage response by mediating the ubiquitin- proteasome degradation of the DNA repair protein NABP2 (PubMed:25249620). {ECO:0000269|PubMed:17532294, ECO:0000269|PubMed:19762596, ECO:0000269|PubMed:19762597, ECO:0000269|PubMed:32126207}. This is the function of FBXL5 (F-box and leucine rich repeat protein 5, ENSG00000118564).