ZPR1 and proximal spinal muscular atrophy: These findings suggest that: (i) ZPR1 deficiency contributes to SMA pathogenesis via R-loop-mediated DNA damage leading to genomic instability and neurodegeneration; and (ii) ZPR1 rescues DNA damage by preventing the accumulation of pathogenic R-loops and may act as a protective modifier of SMA (Kannan et al., 2020; Cuartas and Gangwani, 2022).