In this study, the cells from three HSP patients carrying SPG3a mutations and two carrying SPG4 mutations were compared to three different CTRL hiPSC lines and used to generate patient-specific motor units composed of lower MNs able to reach myotubes and generate motor function units, also called NMJs, characterized by the co-localization of NEFH with clusters of α-Bungarotoxin (Bgt)-positive AChRs on the surface of ACTN2-stained myotubes. Here, ATL1 is linked to hereditary spastic paraplegia.