RBMXL1 is an RNA-binding protein that functions as a retrogene of RBMX, sharing >95% sequence identity 1. As a key post-transcriptional regulator, RBMXL1 participates in pre-mRNA splicing and mRNA binding 2. In myeloid leukemia, RBMXL1 and RBMX are overexpressed and required for leukemogenesis; they directly bind mRNAs and regulate transcription of multiple loci including CBX5 (HP1α), controlling chr1 state and leukemia cell survival 2. RBMXL1 expression is subject to translational regulation through alternative splicing of its 5'-UTR, which creates upstream open reading frames (uORFs) in activated B lymphocytes following EBV infection or CD40/IL-4 activation, providing fine-tuning of RBMX/RBMXL1 protein levels 1. Beyond malignancy, RBMXL1 contributes to heterochromatin maintenance by impeding alternate fate gene activation during cellular reprogramming 3. Clinically, RBMXL1 dysregulation associates with acute myeloid leukemia progression and represents a therapeutic target 2. Additionally, RBMXL1 variants showed nominal association with exceptional longevity in centenarians 4, and mutations have been identified in cutaneous melanoma and lung adenocarcinoma 5, 6, suggesting broader roles in cancer biology.