EPB41L4A (erythrocyte membrane protein band 4.1 like 4A) is a gene involved in cytoskeletal organization, with its antisense RNA transcript (EPB41L4A-AS1) emerging as a significant regulatory element in disease processes. The EPB41L4A locus contains a highly conserved topologically associating domain (TAD) boundary present in both human chromosome 5 and mouse chromosome 5 1. Structural variants at this locus can disrupt TAD architecture, leading to dysregulation of the Nrep gene, which plays a crucial role in nervous system development, potentially contributing to neurodevelopmental phenotypes including dyslexia and intellectual disability 1. Mutations in EPB41L4A have been identified as causative in neurogenetic disorders through whole-exome sequencing studies of consanguineous families 2. The antisense RNA EPB41L4A-AS1 functions as a tumor suppressor across multiple cancers, including breast cancer, non-small-cell lung cancer, and gastric cancer, where it regulates cell proliferation, apoptosis, and metastasis through various miRNA-mediated pathways 345. Additionally, EPB41L4A-AS1 serves as a diagnostic biomarker and therapeutic target in chr5 periodontitis, osteosarcoma, and age-related diseases, modulating inflammatory responses, osteogenic differentiation, and cellular metabolism 678.