F-box and leucine-rich repeat protein 18 (FBXL18)

F-box and leucine-rich repeat protein 18 (FBXL18) is an E3 ubiquitin ligase that functions as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex[3]. It mediates ubiquitination and subsequent proteasomal degradation or stabilization of specific substrate proteins, notably including FBXL7 (a pro-apoptotic factor), RPS15A (a ribosomal protein), and AKT (a kinase involved in cell survival signaling)[1][2][5]. By targeting these proteins, FBXL18 plays a regulatory role in apoptosis, cell cycle progression, and cell proliferation. FBXL18 has been shown to be highly expressed in several cancers (such as hepatocellular carcinoma and glioma) and is linked to poor prognosis, with evidence supporting its role as an independent oncogenic driver in certain contexts[1]. It is also implicated in neurodegenerative diseases such as Parkinson’s disease, through regulation of neuronal toxicity. The FBXL18/RPS15A/SMAD3 axis in particular has been identified as a potential therapeutic target in hepatocellular carcinoma[1]. No approved drugs are currently known to selectively target FBXL18, but its expression and activity offer potential as a prognostic marker and future drug target.

Other names

F-box/LRR-repeat protein 18FBXL18FBL18FLJ11467Fbl18

Promotion of K63-linked ubiquitination of select substrates (e.g., RPS15A, AKT, FBXL7); Mediation of target protein degradation via the proteasome