RBMXL3 is a primate-specific RNA-binding protein that regulates pulmonary surfactant protein B (SP-B) mRNA stability through glucocorticoid signaling 1. The protein binds to a 30-nucleotide hairpin element (RBE) in the 3'-untranslated region of human SP-B mRNA, and this interaction is enhanced by dexamethasone treatment 1. In the absence of glucocorticoid stimulation, cellular mRNA decay factors occupy the RBE and reduce SP-B mRNA stability; dexamethasone-enhanced RBMXL3 binding displaces these factors, thereby stabilizing the transcript 1. Beyond its characterized lung function, RBMXL3 has been identified as a candidate gene in male infertility. It was recurrently detected in patients with primary male infertility and nonobstructive azoospermia (NOA) 234, suggesting a role in spermatogenesis, though the precise mechanism remains undefined. RBMXL3 mutations have also been identified in neuroblastoma and dilated cardiomyopathy cases 56. The protein's functions align with its annotated roles in RNA binding and mRNA splicing, though clinical significance of non-pulmonary RBMXL3 variants requires further characterization.