The endo-lysosomal transmembrane protein 106B (TMEM106B) is among this elite group, having been first been as a risk modifier of frontotemporal lobar degeneration (FTLD) (Van Deerlin et al., 2010), and subsequently as a modifier of numerous other neurodegenerative disorders including Alzheimer’s disease (AD) (Jun et al., 2016; Milind et al., 2020), hippocampal sclerosis (Rutherford et al., 2012; Murray et al., 2014; Nelson et al., 2015), and cognitive decline in amyotrophic lateral sclerosis and Parkinson’s disease (Vass et al., 2011; Tropea et al., 2019) for review see (Feng et al., 2021). This evidence concerns the gene TMEM106B and early-onset autosomal dominant Alzheimer disease.