HNRNPUL2 is a heterogeneous nuclear ribonucleoprotein that functions as an RNA-binding protein localized to the nucleus and nucleoplasm, where it participates in alternative mRNA splicing and RNA regulation 1. Mechanistically, HNRNPUL2 regulates DNA-end resection by binding to the MRE11-RAD50-NBS1 (MRN) complex and promoting ATR-dependent signaling and homologous recombination-mediated DNA double-strand break (DSB) repair 2. Additionally, HNRNPUL2 regulates innate immune responses by accumulating in the nucleus where it binds the Nlrp3 promoter to control macrophage pyroptosis, with formononetin inhibiting this nuclear accumulation 3. HNRNPUL2 also stabilizes the long noncoding RNA CRNDE in the cytoplasm, thereby promoting colorectal cancer cell proliferation via Ras/MAPK pathway activation 4. Disease relevance includes autism, where loss-of-function HNRNPUL2 variants represent a moderate-risk genetic factor associated with less severe cognitive impairment compared to highly penetrant autism genes 1. HNRNPUL2 expression also predicts poor prognosis in chr11 lymphocytic leukemia and other cancers 5, and rare variants are associated with childhood-onset systemic lupus erythematosus 6. A conserved upstream ORF in HNRNPUL2 expressed in human lymphocytes may harbor additional biological functions 7.