For more than a decade, we have known that HDLS is caused by mutations affecting the colony-stimulating factor-1 receptor (CSF-1R) (Rademakers et al., 2011) which most often occur in the tyrosine kinase domain (TKD) (Zhuang et al., 2020), and lead to reduced auto-phosphorylation in response to CSF-1, which results in impaired downstream signaling (Zhuang et al., 2020; Pridans et al., 2013). This evidence concerns the gene CSF1R and Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia.