Although similar amounts of both wildtype and mutant RNA were injected, we cannot exclude the possibility that these differences are owing to reduced RNA stability rather than aberrant protein function of the mutant RNF170. The autosomal recessive mode of inheritance in family B with absence of features associated with HSP in heterozygous mutation carriers (e.g., B.1, B.2) as well as the absence of detectable expression of RNF170Cys102Arg after overexpression in SH-SY5Y(RNF170ko) cells (Fig. 3e) also argue against a clinically relevant dominant-negative effect of the p.Cys102Arg mutation. Here, RNF170 is linked to hereditary spastic paraplegia.