SACS encodes sacsin, a co-chaperone that regulates Hsp70 chaperone machinery and facilitates protein folding 1. The protein localizes to multiple cellular compartments including mitochondria, nucleus, cytoplasm, and axons, where it binds Hsp70 proteins and participates in protein-folding processes and proteasome interactions. SACS negatively regulates inclusion body assembly, suggesting a role in preventing protein aggregation [UniProt annotations]. Mutations in SACS cause autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disease characterized by early-onset cerebellar ataxia, pyramidal spasticity, and demyelinating neuropathy 1. Neuropathologically, ARSACS involves Purkinje cell death, superior cerebellar vermis atrophy, pyramidal degeneration, and motor neuron loss 1. SACS mutations rank among the most frequently identified causes of recessive ataxia, with diagnostic prevalence of 8/319 (2.5%) in ataxia cohorts and 5/6 (83.3%) in spasticity cases 2. Recently, novel SACS variants have been identified in peripheral neuropathy patients with spasticity 3. Currently, no effective therapy exists for ARSACS, though induced pluripotent stem cell models derived from patient cells offer promising avenues for mechanistic investigation and therapeutic discovery.