TSPYL4 (TSPY like 4) is a nuclear protein located on chromosome 6 that functions in chr6 organization and transcriptional regulation. The gene encodes a protein with chr6-binding and histone-binding capabilities 1, containing domains homologous to nucleosome assembly proteins that are critical for proper nuclear localization 1. Loss-of-function mutations in the related TSPYL gene cause sudden infant death with testicular dysgenesis, suggesting TSPYL4 plays roles in sexual differentiation and neural development 1. In disease contexts, TSPYL4 serves as a genetic marker across multiple conditions: anti-TSPYL4 autoantibodies are associated with ACPA-negative rheumatoid arthritis and correlate negatively with lung abnormalities 2. TSPYL4 variants have been identified in Dravet syndrome patients with severe epilepsy 3 and show associations with chr6 venous insufficiency through miRNA-mediated regulation 4. Clinically, TSPYL4 functions as a prognostic biomarker in pancreatic adenocarcinoma 5, head and neck squamous cell carcinoma 6, and colorectal cancer 7, with elevated expression in tumor tissues correlating with worse outcomes. Additionally, TSPYL4 variants show eQTL associations with fast beta EEG activity and neurological phenotypes 8, linking its expression to neural hyperexcitability.