PIKFYVE and Alzheimer disease: Remarkably, we demonstrated for the first time that TRPML1 activation, via the small-molecule agonist ML-SA1 (Fine et al., 2020; Grimm et al., 2010; Shen et al., 2012), overrides the PI(3,5)P2 deficit-induced defects caused by PIKfyve inhibition in neurons and protects against multiple AD-related EAL neuropathologies.