SPAST and Spastic paraplegia: We demonstrate that the transcription factors (TFs) NRF1 and SOX11 as well as the microRNAs (miRNAs) miR-182 and miR-96 are major factors involved in the regulation of SPAST. These findings provide a foundation for understanding regulation of spastin expression, identify new target sequences for mutation screening at the SPG4 locus, and suggest novel approaches to consider for therapeutic approaches in dominantly inherited spastic paraplegia.