ZSCAN20 is a zinc finger transcription factor with emerging roles in immune regulation and disease pathogenesis. Primary function: ZSCAN20 acts as a DNA-binding transcription factor with RNA polymerase II-specific activity 1. Mechanism: Recently discovered as a TEXterm-selective transcription factor, ZSCAN20 promotes terminal exhaustion of CD8+ T cells, a dysfunctional state characterized by upregulation of inhibitory receptors 1. Targeted deletion of ZSCAN20 in T cells reduces inhibitory receptor expression and improves effector function, while enhancing tumor control and synergizing with immune checkpoint blockade 1. Disease relevance: ZSCAN20 has been implicated in multiple conditions including hepatocellular carcinoma, where elevated expression correlates with poor prognosis and associates with cell cycle progression, immune infiltration, and m6A RNA modifications 2. ZSCAN20 variants also show suggestive associations with circulating fibroblast growth factor 21 levels 3 and sex-specific association with diabetic neuropathic pain susceptibility 4. Clinical significance: As an independent prognostic biomarker in hepatocellular carcinoma 2, ZSCAN20 represents a potential therapeutic target for enhancing anti-tumor immunity through T cell engineering and may inform stratification strategies in cancer immunotherapy.