NIF3L1 (NGG1 interacting factor 3 like 1) is a highly conserved protein encoded on chromosome 2, with orthologs spanning bacteria to mammals 1. The protein localizes primarily to the cytoplasm but translocates to the nucleus during specific cellular processes 12. NIF3L1 functions as a transcriptional corepressor through cooperation with Trip15/CSN2 (COPS2), a component of the COP9 signalosome 2. This interaction negatively regulates neural differentiation by suppressing pluripotency factors (Oct-3/4) while inducing neuronal specification markers (Mash-1) 2. NIF3L1 interacts with itself and with NIF3L1 BP1, a novel cytoplasmic binding partner containing a putative leucine zipper domain, suggesting roles in protein complex formation 3. The protein exhibits ubiquitous expression throughout embryonic development and adult tissues, with particularly high levels in germ cell lineages 14. NIF3L1 also interacts with WBSCR14 and 14-3-3 proteins, affecting subcellular localization of transcriptional complexes 5. During sperm capacitation, NIF3L1 surface abundance increases through ubiquitin-proteasome system regulation, potentially influencing male gamete fertility 6. While highly conserved evolutionarily, NIF3L1 is not associated with amyotrophic lateral sclerosis despite mapping to the ALS2 critical region 7.