Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation. Plays a role in targeting endocytosed EGFR and ERGG3 for lysosomal degradation, and thereby helps down-regulate downstream signaling cascades (PubMed:23166352). Helps recruit the ESCRT complex components TSG101, HGS and STAM to cytoplasmic membranes. Probably plays a role in regulating protein degradation via its interaction with NEDD4 (By similarity). May also contribute to the regulation of gene expression in the nucleus. Binds DNA (in vitro) and may play a synergistic role with STAT6 in the nucleus in regulating the expression of various cytokines (PubMed:15793005, PubMed:21980379). May regulate the expression of numerous cytokines, such as TNF, CCL2, CCL5, CXCL1, IL1A and IL10 (PubMed:12355436, PubMed:15025820, PubMed:16954198, PubMed:21980379, PubMed:22160695). Monomer. Interacts with NEDD4 (PubMed:11042109). Interacts (via PSAP motif) with TSG101, a component of the ESCRT-I complex (endosomal sorting complex required for transport I). Interacts with WWOX. Interacts with STAM, a component of the ESCRT-0 complex; the interaction is direct. Identified in a complex with STAM and HGS; within this complex, interacts directly with STAM, but not with HGS. Interacts with STAT6 (PubMed:15793005). Associated with membranes of lysosomes, early and late endosomes. Can translocate from the cytoplasm into the nucleus (By similarity). Detected at Schmidt-Lanterman incisures and in nodal regions of myelinating Schwann cells (PubMed:22729949). Detected in brain, heart, lung, liver, spleen and bone marrow (PubMed:22160695). Detected in myelinating Schwann cells in sciatic nerve and in bone marrow-derived macrophages (at protein level) (PubMed:22729949). Widely expressed. Highly expressed in liver. Expression in sciatic nerve is low in neonates, culminates seven days after birth and decreases rapidly thereafter (at protein level) (PubMed:22729949). Strong expression is detected at E.7 and drops at 11 dpc. Up-regulated in macrophages exposed to lipopolysaccharide (LPS) (at protein level) (PubMed:15793005). By estrogen and lipopolysaccharides (LPS). The PPxY motif mediates interaction with WWOX and NEDD4. The LITAF domain is stabilized by a bound zinc ion. The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes. It interacts specifically with phosphatidylethanolamine lipid headgroups, but not with phosphoglycerol, phosphocholine, phosphoserine or inositolhexakisphosphate. Phosphorylated on tyrosine residues in response to EGF. No visible phenotype. Mice are born at the expected Mendelian rate and are fertile. Mutant mice display altered responses to nerve crush injury, with higher numbers of macrophages in injured nerves five days after nerve crush injury, but at later time points macrophage numbers in injured nerves are normal. Bone marrow-derived macrophages from mutant mice display increased migration in response to CCL3, but not in the absence of CCL3 (PubMed:22729949). Mutant mice show dramatically increased survival in response to a dose of lipopolysaccharide (LPS) that causes rapid death of 40% of wild-type mice (PubMed:22160695). Belongs to the CDIP1/LITAF family.