Presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

Hereditary spastic paraplegia(HSP)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower limbs.Pat ients can also experience peripheral neuropathy,cognitive impairment,and other neurological symptoms.To date,more than 80 genes have been implicated in HSP,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(Parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HSP.