Through lipidomic analysis of DDHD2 knock-out mice, Inoles and colleagues determined that DDHD2 is a neuron-specific triglyceride lipase (Inloes et al., 2014), and loss of this enzyme’s activity leads to a massive accumulation of triglyceride-containing lipid droplets throughout neurons in the brain, consistent with the fact that hereditary spastic paraplegia-54 patients have large lipid accumulations in their brains (Thabet et al., 2020). Here, DDHD2 is linked to hereditary spastic paraplegia.