IGHMBP2 is a 5' to 3' RNA/DNA helicase that unwinds nucleic acid duplexes in an ATP-dependent manner, with specificity for 5'-phosphorylated guanine-rich sequences 1. The protein appears multifunctional, participating in ribosome biogenesis, translation initiation, and RNA metabolism 2, while also potentially regulating transcription 3. IGHMBP2 interacts with tRNA and associates with the activator of basal transcription (ABT1) protein, influencing pre-rRNA processing 4. Mutations in IGHMBP2 cause two distinct autosomal recessive neurological diseases with different severity profiles. Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a severe, fatal neurodegenerative disorder characterized by progressive motor neuron loss and respiratory failure, while Charcot-Marie-Tooth disease type 2S (CMT2S) presents as a milder, non-fatal peripheral neuropathy 56. Disease severity correlates with the degree of biochemical impairment: D565N mutations (SMARD1-associated) severely reduce IGHMBP2 helicase and ATPase activities, while H924Y mutations (CMT2S-associated) cause lesser activity reduction 47. Compound heterozygous mutations demonstrate intermediate biochemical profiles that correlate with intermediate disease phenotypes 7. Therapeutic approaches may require mutation-specific interventions based on residual IGHMBP2 biochemical activity 4.