Several mutations of KIF5A neck and motor domain leading to HSP have been characterized in detail in vitro and have been found to exhibit reduced ATPase activity, microtubule affinity and gliding velocity, which affect the processivity and directionality of the motor and can result in reduced cargo flux and consequent deficient synaptic supply (Ebbing et al., 2008; Goizet et al., 2009; Jennings et al., 2017; Dutta et al., 2018). The gene discussed is KIF5A; the disease is hereditary spastic paraplegia.