NFXL1 (nuclear transcription factor, X-box binding like 1) is a transcription factor containing NFX1-type zinc finger domains that mediate DNA binding 1. The protein is ubiquitously expressed across human tissues, with notably high expression in the cerebellum 2. Despite GO annotations indicating nuclear localization and RNA polymerase II-specific transcription regulatory activity, immunofluorescence studies demonstrated cytoplasmic localization in HEK and SH-SY5Y cells, suggesting that nuclear translocation may require specific cellular conditions 2. NFXL1 variants are implicated in neurodevelopmental and psychiatric disorders. Heterozygous coding variants confer increased risk for specific language impairment (SLI) in complex genetic models 3, and a homozygous missense variant (c.1322G>A; p.Cys441Tyr) segregated with treatment-resistant psychosis/schizophrenia in consanguineous families 4. Additionally, homozygous NFXL1 variants have been identified in a novel recessive syndrome characterized by hyperlaxity, short stature, and kidney disease 5. These findings establish NFXL1 as a functionally important transcription factor with significant roles in neurodevelopmental and systemic disorders, though its precise molecular mechanisms require further investigation.