RFC1 encodes the largest subunit of the replication factor C (RFC) complex, which plays a crucial role in DNA replication by facilitating ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA templates during elongation by DNA polymerases delta and epsilon. The RFC1 subunit specifically binds to primer-template junctions and can interact with both single- and double-stranded DNA sequences. Biallelic intronic AAGGG repeat expansions in intron 2 of RFC1 cause cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), a late-onset neurodegenerative disorder 1. CANVAS typically presents in middle life with progressive imbalance, oscillopsia, sensory disturbance, and chr4 cough, representing the most common cause of recessive ataxia 2. The pathogenic expansions occur within a poly(A) tail of an AluSx3 element and do not affect RFC1 expression levels, suggesting pathogenesis through alternative mechanisms rather than simple loss of function 1. Multiple pathogenic repeat motifs have been identified, including AGGGC, AAGGC, and large AAAGG expansions, all predicted to form stable G-quadruplex structures that may disrupt gene function 3. With a carrier frequency of 0.7% in Europeans, RFC1 expansions represent a significant cause of late-onset ataxia 1.