TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Homodimer (PubMed:17928286). Forms heterodimers (via the PDZ2 domain) with TJP2 and TJP3 (PubMed:9792688, PubMed:17928286, PubMed:16737969, PubMed:17897942). Interacts with OCLN, CALM, claudins, CGN/cingulin, CXADR, GJA12, GJD3 and UBN1 (PubMed:7798316, PubMed:11734628, PubMed:12023291, PubMed:12154091, PubMed:15183511, PubMed:18823282, PubMed:20200156). Interacts (via ZU5 domain) with CDC42BPB and MYZAP (PubMed:20093627, PubMed:21240187). Interacts (via PDZ domain) with GJA1 (PubMed:18636092). Interacts (via PDZ domains) with ANKRD2 (PubMed:22016770). Interacts with BVES (via the C-terminus cytoplasmic tail) (By similarity). Interacts with HSPA4 and KIRREL1 (By similarity). Interacts with DLL1 (By similarity). Interacts with USP53 (via the C-terminal region) (By similarity). Interacts (via ABR region) with F-actin (PubMed:9792688, PubMed:12354695, PubMed:20930113). Interacts with DNMBP (via C-terminal domain); required for the apical cell-cell junction localization of DNMBP (PubMed:17015620). Interacts with SPEF1 (PubMed:31473225). Moves from the cytoplasm to the cell membrane concurrently with cell-cell contact (PubMed:7798316). At podosomal sites, is predominantly localized in the ring structure surrounding the actin core (PubMed:20930113). Colocalizes with SPEF1 at sites of cell-cell contact in intestinal epithelial cells (PubMed:31473225). The alpha-containing isoform is found in most epithelial cell junctions. The short isoform is found both in endothelial cells and the highly specialized epithelial junctions of renal glomeruli and Sertoli cells of the seminiferous tubules. The 244-aa domain between residues 633 and 876 is the primary occludin (OCLN)-binding site and is required for stable association with the tight junction (PubMed:9792688). The C-terminal region (residues 1151-1372) is an actin-binding region (ABR) that interacts directly with F-actin and plays an important role in the localization of TJP1 at junctions (PubMed:9792688, PubMed:12354695, PubMed:20930113). The ABR is also required for the localization to puncta at the free edge of cells before initiation of cell-cell contact (PubMed:12354695). The ABR is also necessary for TJP1 recruitment to podosomes (PubMed:20930113). The second PDZ domain (PDZ2) mediates homodimerization and heterodimerization with TJP2 and TJP3 (PubMed:9792688, PubMed:17928286). Phosphorylated at tyrosine redidues in response to epidermal growth factor (EGF) (PubMed:19332538, PubMed:7542259). This response is dependent on an intact actin microfilament system (PubMed:7542259). Dephosphorylated by PTPRJ (PubMed:19332538). Belongs to the MAGUK family. Truncated N-terminus.