Considering that both atRA-signaling and synaptopodin-mediated signaling pathways have been associated to pathological brain states, such as Alzheimer’s disease (Endres, 2019; Fahrenholz et al., 2010; Goetzl et al., 2016; Aloni et al., 2019; Wingo et al., 2019), we are confident that a better understanding of atRA-mediated synaptopodin-dependent synaptic plasticity may support the development of novel therapeutic strategies aimed at synaptic plasticity modulation. Here, SYNPO is linked to early-onset autosomal dominant Alzheimer disease.