Ca2+ mishandling and MAMs alterations may be involved in the pathogenic mechanism of two other genes causing complex syndromes with optic atrophy, i.e., Ubiquitin C-Terminal Hydrolase L1 (UCHL1) and RTN4IP. Homozygous or compound heterozygous mutations in the UCHL1 gene, encoding for a neuronal specific deubiquitinating enzyme, have been associated to early-onset spastic paraplegia and optic atrophy, with additional variable features such as peripheral neuropathy, cerebellar ataxia, myokymia, and cognitive impairment [232,233], a phenotype resembling that of Uchl1 knockout mice [234,235]. This evidence concerns the gene UCHL1 and Spastic paraplegia.