HNRNPDL (heterogeneous nuclear ribonucleoprotein D like) is a multifunctional RNA-binding protein that regulates both transcription and RNA processing. The protein extensively controls gene expression and alternative splicing of hundreds of genes involved in transcription regulation and critical signaling pathways including NOD-like receptor, Notch, and TNF signaling 1. HNRNPDL functions as a transcriptional regulator and binds to AU-rich elements in mRNAs, influencing post-transcriptional control. Mechanistically, HNRNPDL can form functional amyloid fibrils through its Gly/Tyr-rich domain, with RNA-binding domains arranged as a solenoidal coat around the amyloid core, allowing continued nucleic acid binding 2. The protein undergoes ubiquitin-mediated degradation regulated by TRIM4, which affects cellular sensitivity to CDK4/6 inhibitors in cancer 3. Disease relevance centers on limb-girdle muscular dystrophy D3 (LGMD D3), caused by mutations at codon 378, particularly c.1132G>A and c.1132G>C variants 4. Clinically, HNRNPDL-related LGMD D3 presents with variable phenotypes from proximal limb-girdle weakness to distal involvement, characterized by scapular winging and distinctive muscle MRI patterns showing adductor magnus involvement while sparing rectus femoris 4. The disease involves autophagic mechanisms with rimmed vacuoles in muscle biopsies.