CCNF encodes cyclin F, a substrate recognition component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates ubiquitination and proteasomal degradation of target proteins 1. The SCF(CCNF) complex functions as an integral component of the ubiquitin proteasome system, linking protein degradation to cell cycle regulation 1. Cyclin F targets various proteins involved in cell cycle progression and genome stability, including CP110, RRM2, and CDC6 during G2 phase to prevent centrosome reduplication and DNA re-replication 1. Pathogenic mutations in CCNF cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), with frequencies ranging from 0.6-1.1% in different populations 234. Disease-causing mutations like p.S621G disrupt normal ubiquitin homeostasis, leading to elevated Lys48-linked ubiquitination and defective autophagy in neuronal cells 15. These mutations cause ubiquitin-proteasome system dysfunction in motor neurons, resulting in accumulation of ubiquitinated protein inclusions characteristic of ALS/FTD pathology 5. The identification of CCNF mutations has expanded understanding of ALS pathogenesis and highlighted the critical role of protein quality control mechanisms in neurodegeneration 6.