SMN1 and proximal spinal muscular atrophy: The primary role of SMN protein is to facilitate snRNP assembly by forming SMN complex with Gemins2-8 and Unrip.33,53 snRNPs are major components of the spliceosome which regulate pre-mRNA splicing.54,55 Loss of SMN altered the stoichiometry of snRNAs and caused widespread defects in pre-mRNA splicing in numerous transcripts of diverse genes in SMA mouse models.9,56 As revealed by RNA and single-cell sequencing analysis, SMN is implicated in differentiation of hypertrophic chondrocytes through alternative splicing, yet the key molecules acting downstream of SMN remain elusive.