TDP43 (TAR DNA-binding domain protein 43) and FUS/TLS (fused in sarcoma/translated in liposarcoma) are RNA-binding proteins that are predominantly located in the nucleus and play a role in regulating RNA metabolism. Studies have shown that abnormal accumulation of FUS/TLS and TDP43 in the cytosol directly leads to the misfolding of wtSOD1 (wild-type Cu/Zn superoxide dismutase) in non-SOD1 FALS (familial ALS) and SALS (sporadic ALS), which means that they constitute common molecular pathogenesis mechanisms of ALS.59 A previous study found that lncRNA could recruit FUS/TLS to the genomic locus that encodes cyclin D1, where cyclin D1 transcription is repressed in response to DNA damage signals, resulting in increased tolerance to apoptosis signals and indicating that lncRNA may play a role in pathological changes in ALS (Figure 4).60, 61Figure 4Role of lncRNAs in ALSlncRNA could recruit FUS/TLS to the genomic locus that encodes cyclin D1, where cyclin D1 transcription is repressed in response to DNA damage signals, resulting in increased tolerance to apoptosis signals.