LIG4 and amyotrophic lateral sclerosis: Although initially the connection between TDP43 dysfunction and the accumulation of GIN in ALS was thought to be a secondary feature, recent evidence shows that neuronal TDP43 plays an important direct role in DDR by controlling the nuclear recruitment of the XRCC4-DNA ligase 4 (LIG4) complex, critical for DSB repair via NHEJ [63].