Using human stem cell-based models of SPG3A, a recent study reported the lipid deficiency caused by ATL1 mutations lead to axonal degeneration of human cortical projection neurons (Mou et al., 2020), providing evidence to support the direct interactions between neuron and astrocytes in HSP human models, opening new opportunities for studying HSP. This evidence concerns the gene ATL1 and hereditary spastic paraplegia.