Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5-ATG12-ATG16L E3-like ligase, SQSTM1 and LC3. Involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures) (By similarity). Important for normal brain development (PubMed:25198012, PubMed:27648578). Essential for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Involved in the ability of neural cells to respond to guidance cues. Required for cortical neurons to respond to the trophic effects of netrin-1/NTN1 (PubMed:27648578). Regulates Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner. This process may be important for the determination of brain size during embryonic development (By similarity). May regulate osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (PubMed:27330028). After cytokinetic abscission, involved in midbody remnant degradation. In vitro strongly binds to phosphatidylinositol 3-phosphate (PtdIns3P) (By similarity). Directly interacts with ATG5 and associates with the ATG12-ATG5-ATG16L complex. Interacts with p62/SQSTM1. Directly interacts with GABARAP, GABARAPL1 and GABARAPL2; the interaction with GABARAP is required for WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies. Weakly interacts with MAP1LC3C; this interaction is direct. Does not interact with MAP1LC3A, nor MAP1LC3B (By similarity). Interacts with TRAF6 (PubMed:27330028). Relocalization from the nucleus to the cytosol is stimulated by cellular stress, such as starvation or proteasomal inhibition. In the cytosol of starved cells, colocalizes with autophagic structures. This redistribution is dependent on p62/SQSTM1. When nuclear export is blocked by treatment with leptomycin B, accumulates in nuclear bodies, that completely or partially colocalize with promyelocytic leukemia (PML) bodies (By similarity). Localizes throughout neurons, including within axons. In neurons, enriched in the light membrane fraction along with the synaptosomal membrane protein synaptophysin and the membrane-bound form of LC3/MAP1LC3A/MAP1LC3B, called LC3-II, a classic marker for autophagic vesicles (PubMed:27648578). Widely expressed, with high levels in the brain (at protein level) (PubMed:15342963, PubMed:15292400, PubMed:27648578). In the brain, expressed by both neuronal and non-neuronal cells (PubMed:27648578). Expressed in bones, in the periosteum, cartilage, growth plate, trabeculae of the primary spongiosa, and scattered hematopoietic cells within the medullary cavity. Tends to be expressed at lower levels in the hypertrophic zone compared to trabeculae. Expressed in osteoblasts, osteoclasts and bone-marrow derived macrophages (PubMed:27330028). Detected in the developing central nervous system already at 11.5 dpc (PubMed:27648578). At 13.5 dpc, strong expression in the proliferative zones surrounding the lateral ventricle and weaker expression throughout the developing forebrain. At 14.5 dpc, highest expression within the proliferative regions surrounding the ventricles. Specifically expressed in the leptomeninges, cortical intermediate zone, choroid plexus and in radial glia cells within the ventricular zone (VZ). Within the VZ, expression is observed in a subset of cells actively undergoing mitosis. The expression persists through all phases of cell division, but decreases during telophase. Expression is often maintained in radial units, where it is the highest in progenitors closest to the ventricle, then gradually diminishes as distance from the ventricular surface increases (PubMed:15342963, PubMed:25198012). Expression levels in the brain decrease after birth (at protein level) (PubMed:15342963). The LIR (LC3-interacting region) motif mediates the interaction with MAP1LC3C and other ATG8 family members. The FYVE domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns3P). Homozygous mice are born at close to the expected Mendelian ratios, but die perinatally (PubMed:25198012, PubMed:27648578). Newborn animals exhibit striking abnormalities in the forebrain, midbrain and hindbrain, including visibly smaller brains and gross enlargement of the lateral ventricles. There is an apparent loss and disorganization of interhemispheric axonal tracts throughout the brain (PubMed:25198012, PubMed:27648578).