Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures) and links ALIS to the autophagic machinery (By similarity). Involved in midbody ring degradation (By similarity). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:11244088, PubMed:11500922). May play a role in titin/TTN downstream signaling in muscle cells (By similarity). May regulate signaling cascades through ubiquitination (By similarity). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels (By similarity). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (By similarity). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (By similarity). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (By similarity). More potent than isoform 2 to stimulate PRKCZ-dependent phosphorylation of KCNAB2. Homooligomer or heterooligomer; may form homotypic arrays. Interacts directly with PRKCI and PRKCZ (Probable). Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1, NTRK2, NTRK3, TRIM13, MAP2K5 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. Forms a complex with MAP2K5 and PRKCZ or PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1 probably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with AJUBA, PRKCZ and TRAF6. Interacts with TRAF6 and CYLD. Identified in a complex with TRAF6 and CYLD. Identified in a heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule (By similarity). Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3. Interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6. Interacts with NGFR through TRAF6 and bridges that complex to NTRK1. Interacts with NBR1 and TRIM55. Directly interacts with MAP1LC3A and MAP1LC3B, as well as with other MAP1 LC3 family members, including GABARAP, GABARAPL1 and GABARAPL2; these interactions are necessary for the recruitment MAP1 LC3 family members to inclusion bodies containing polyubiquitinated protein aggregates and for their degradation by autophagy (By similarity). Interacts with FHOD3 (By similarity). Interacts with TRMI5 (By similarity). Interacts with SESN1 (By similarity). Interacts with SESN2 (By similarity). Interacts with ULK1. Interacts with UBD (By similarity). Interacts with WDR81; the interaction is direct and regulates the interaction of SQSTM1 with ubiquitinated proteins (By similarity). Interacts with WDFY3; this interaction is required to recruit WDFY3 to cytoplasmic bodies and to PML bodies (By similarity). Interacts with TRIM23 (By similarity). Interacts with LRRC25 (By similarity). Interacts with TRIM50 (By similarity). Interacts with TRIM16 (By similarity). Interacts with STING1; leading to relocalization of STING1 to autophagosomes (By similarity). Interacts (when phosphorylated at Ser-348) with KEAP1; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering KEAP1 in inclusion bodies, promoting its degradation (By similarity). Interacts with GBP1 (By similarity). Interacts with MOAP1; promoting dissociation of SQSTM1 inclusion bodies that sequester KEAP1 (By similarity). In cardiac muscles, localizes to the sarcomeric band. Localizes to late endosomes. May also localize to the nucleus. Colocalizes with TRIM13 on the perinuclear endoplasmic reticulum (By similarity). Commonly found in inclusion bodies containing polyubiquitinated protein aggregates (By similarity). Co-localizes with TRIM5 in cytoplasmic bodies (By similarity). When nuclear export is blocked by treatment with leptomycin B, accumulates in PML bodies (By similarity). Ubiquitously expressed. In brain, mainly expressed by neurons, especially pyramidal neurons in the cerebral cortex and hippocampus. Also expressed by Purkinje cells and neurons in the dentate nucleus of the cerebellum and neurons of the basal ganglia (at protein level). Maximal expression is detected at postnatal day 13 (P13) (at protein level). By the proteasome inhibitors MG132 and lactacystin. By intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC). By okadaic acid and kainate (at protein level). Isoform 1 and isoform 2 relative amounts are changed upon up-regulation of the expression by NGF. The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the UBA and PB1 domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies. The PB1 domain mediates homooligomerization and interactions with FHOD3, MAP2K5, NBR1, PRKCI, PRKCZ and WDR81. Both the PB1 and UBA domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies. The ZZ-type zinc finger mediates the interaction with RIPK1. The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. Phosphorylated (PubMed:9177193). Phosphorylated in vitro by TTN (By similarity). May be phosphorylated by PRKCZ. Phosphorylation at Ser-402 by ULK1 is stimulated by SESN2 (By similarity). Phosphorylated at Ser-402 by TBK1, leading to promote relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (By similarity). Phosphorylation at Ser-348 by MTOR promotes interaction with KEAP1 and inactivation of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (By similarity). Ubiquitinated by UBE2J1 and RNF26 at Lys-434: ubiquitinated SQSTM1 attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport. Deubiquitination by USP15 releases target vesicles for fast transport into the cell periphery. Ubiquitinated by the BCR(KEAP1) complex at Lys-419, increasing SQSTM1 sequestering activity and promoting its degradation. Ubiquitinated via 'Lys-29' and 'Lys-33'-linked polyubiquitination leading to xenophagic targeting of bacteria and inhibition of their replication. Major isoform except in central nervous system.