U2AF1L4 is an RNA-binding protein that functions as a pre-mRNA splicing factor, playing critical roles in both constitutive and alternative splicing processes. The protein enhances accurate 3'-splice site selection by facilitating protein-protein and protein-RNA interactions, particularly by enhancing U2AF2 binding to weak pyrimidine tracts 1. U2AF1L4 specifically participates in alternative splicing regulation, notably activating exon 5 skipping of PTPRC during T-cell activation, an event that can be reversed by GFI1 23. The gene shows coordinated expression with PSENEN through a genuine bidirectional promoter, suggesting their concerted transcription may be necessary for T-cell activity regulation 1. U2AF1L4 expression is regulated by various cytokines including IL-2, IL-7, and IL-15, which have opposite effects on its expression in T cells at different differentiation stages 3. Additionally, human chorionic gonadotropin stimulates U2AF1L4 expression, promoting memory T cell differentiation by increasing CD45R0 expression 2. Recent studies have identified U2AF1L4 as a potential susceptibility risk locus for COVID-19 in South Asian populations and as a hub gene in bicalutamide resistance networks in prostate cancer 45.