Patients with XLF mutations also have immunodeficiency due to a defect in V(D)J recombination, which uses NHEJ to generate diversity in the antibody repertoire of the immune system.

XLF interacts with DNA ligase IV and XRCC4 and is thought to be involved in the end-bridging or ligation steps of NHEJ.

[9] XLF is structurally similar to XRCC4, existing as a constitutive dimer with an N-terminal globular head domain, an alpha-helical stalk, and an unstructured C-terminal region (CTR).

[18] Using a human induced pluripotent stem cell model of NHEJ1 deficiency, it was shown that NHEJ1 has an important role in promoting survival of the primitive hematopoietic progenitors.

[19] These NHEJ1 deficient cells possess a weak NHEJ1-mediated repair capacity that is apparently incapable of coping with DNA damages induced by physiological stress, normal metabolism, and ionizing radiation.