This contrasts with previously identified ALS-associated variants in KIF5A, which are found in the cargo-binding domain, leading to the formation of cytoplasmic aggregates, inclusions of mitochondria, and synaptic vesicles that are toxic to motor neurons through a gain-of-function mechanism [12,13,14], whereas spastic paraplegia and Charcot–Marie–Tooth-associated variants are located in the motor domain. Here, KIF5A is linked to Spastic paraplegia.