The SIGMAR1 selective agonist pridopidine activates the SIGMAR1 by facilitating its dissociation from HSPA5/BiP and enhances the SIGMAR1ʹs innate activity as a chaperone to maintain cellular health against pathological insults like C9orf72 HRE in ALS-FTD. Here, C9orf72 is linked to frontotemporal dementia.