SQSTM1 and amyotrophic lateral sclerosis: In this study, all ALS/FTD-associated p62 mutant proteins, which harbor missense mutations in the LIR and KIR, exhibited increased or decreased binding affinity to their binding partners, LC3 and KEAP1 (Figs. 2 and 3), and some resulted in suppression of p62-mediated NRF2 activation (Fig. 4) and p62 autophagic turnover (Fig. 5).