DNA repair protein involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:17360556, PubMed:27601299, PubMed:27798842, PubMed:27601633, PubMed:27830975, PubMed:28051062, PubMed:29077092, PubMed:30017584). Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends (PubMed:17360556). Interacts with POLL (DNA polymerase lambda); promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL (By similarity). May act in concert with XRCC5-XRCC6 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are non-complementary or partially complementary (PubMed:17360556). Associates with XRCC4 to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (By similarity). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (By similarity). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (By similarity). Binds DNA in a length-dependent manner (By similarity). Homodimer; mainly exists as a homodimer when not associated with XRCC4. Interacts with XRCC4; the interaction is direct and is mediated via a head-to-head interaction between N-terminal head regions. Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Interacts with POLL (DNA polymerase lambda); promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL. Localizes to site of double-strand breaks; recruitment is dependent on XRCC5-XRCC6 (Ku) heterodimer. The coiled-coil region mediates homodimerization. The Leu-lock (Leu-115) site inserts into a hydrophobic pocket in XRCC4. Phosphorylated by PRKDC at the C-terminus in response to DNA damage. Phosphorylation by PRKDC at the C-terminus of XRCC4 and NHEJ1/XLF are highly redundant and regulate ability of the XRCC4-NHEJ1/XLF subcomplex to bridge DNA. Phosphorylation does not prevent interaction with XRCC4 but disrupts ability to bridge DNA and promotes detachment from DNA. Embryonic stem cells are highly sensitive to ionizing radiation and have intrinsic DNA double-strand break repair defects (PubMed:17360556). In contrast, knockout mice only have a relatively mild phenotype with no growth defects, neuronal cell death or overt immunodeficiency (PubMed:18775323). Mature lymphocyte numbers are slightly decreased, and pro-B lines, while ionizing radiation-sensitive, perform V(D)J recombination at nearly wild-type levels (PubMed:18775323). Mice lacking both Paxx and Nhej1/Xlf show embryonic lethality caused by severe defects in classical non-homologous end joining (NHEJ) (PubMed:27601299, PubMed:27798842, PubMed:27601633, PubMed:27830975, PubMed:28051062, PubMed:29077092). Mice lacking both Cyren and Nhej1/Xlf show embryonic lethality caused by severe defects in classical non-homologous end joining (NHEJ) (PubMed:30017584). Belongs to the XRCC4-XLF family. XLF subfamily.