Through its self-oligomerization, p62 is involved in several signal transduction pathways. For example, this protein functions as a signaling hub that may determine whether cells survive by activating the TRAF6-NF-κB pathway, or die by facilitating the aggregation of caspase 8 and the downstream effector caspases [153, 154] . On the other hand, p62 interacts with the Nrf2-binding site on Keap1, a component of the Cullin 3-type ubiquitin ligase for Nrf2, resulting in stabilization of Nrf2 and transcriptional activation of Nrf2 target genes including a battery of antioxidant proteins [155] [156] [157] [158] [159] . It is thus plausible that excess accumulation or mutation of p62 leads to hyperactivation of these signaling pathways, resulting in a disease onset (Figure 3(b) ).