We propose that modulation of cannabinoid receptors will ameliorate T1DM by modulation of the mTORC/TFEB/calcineurin axis (Chiocco et al., 2010; Pan et al., 2020) and promotion of lysosome biogenesis that is a hub for T1DM tolerance, autophagy, and extracellular vesicle signaling. Here, TFEB is linked to type 1 diabetes mellitus.